Microbiology Flashcards

Question

What is the mechanism of action of tetracyclines?

Answer 1

* Reversibly bind to the ribosomal 30S subunit | * Prevent binding of aminoacyl-tRNA to the ribosomal acceptor site, so inhibiting protein synthesis.

Answer 2

They are bacteriostatic and bind to the 50S subunit of the ribosome - interferes with translocation and stimulate dissociation of the peptide-tRNA.

Answer 3

Bacteriostatic and has very broad anti-bacterial activity. It is RARELY USED. It binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation

Answer 4

Risk of aplastic anaemia (1/25,000 – 1/45,000 patients) and grey baby syndrome in neonates because of an inability to metabolise the drug

Answer 5

Binds to the 23S component of the 50S subunit to prevent the formation of a functional 70S initiation complex (required for the translation process to occur).

Answer 6

Highly active against Gram positive organisms, including MRSA and VRE. Not active against most Gram negatives.

Answer 7

Is expensive, may cause thrombocytopoenia and should be used only with consultant Micro/ID approval

Answer 8

Quinolones | Nitroimidazoles

Answer 9

Ciprofloxacin Levofloxacin Moxifloxacin

Answer 10

Metronidazole | Tinidazole

Answer 11

Act on alpha-subunit of DNA gyrase predominantly, but, together with other antibacterial actions, are essentially bactericidal

Answer 12

* Broad antibacterial activity, especially vs Gram –ve organisms, including Pseudomonas aeruginosa * Newer agents (e.g. levofloxacin, moxifloxacin) - increase in activity vs G +ves and intracellular bacteria, e.g. Chlamydia spp

Answer 13

Use for UTIs, pneumonia, atypical pneumonia & bacterial gastroenteritis

Answer 14

* Include the antimicrobial agents metronidazole & tinidazole * Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage * Rapidly bactericidal * Active against anaerobic bacteria and protozoa (e.g. Giardia) * Nitrofurans are related compounds: nitrofurantoin is useful for treating simple UTIs

Answer 15

Rifamycins e.g. rifampicin & rifabutin

Answer 16

* Inhibits protein synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation * Bactericidal * Active against certain bacteria, including Mycobacteria & Chlamydiae * Monitor LFTs * Beware of interactions with other drugs that are metabolised in the liver (e.g oral contraceptives) * May turn urine (& contact lenses) orange

Answer 17

* Except for short-term prophylaxis (vs. meningococcal infection) you should NEVER use as single agent because resistance develops rapidly * Resistance is due to chromosomal mutation. * This causes a single amino acid change in the ß subunit of RNA polymerase which then fails to bind Rifampicin.

Answer 18

Daptomycin – a cyclic lipopeptide with activity limited to G+ve pathogens. Recently licensed antibiotic likely to be used for treating MRSA and VRE Colistin – a polymyxin antibiotic that is active against Gram negative organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella. pneumoniae. It is not absorbed by mouth. It is nephrotoxic and should be reserved for use against multi-resistant organisms

Answer 19

Sulfonamides Diaminopyramidines (e.g. trimethoprim)

Answer 20

* Act indirectly on DNA through interference with folic acid metabolism * Synergistic action between the two drug classes because they act on sequential stages in the same pathway * Sulphonamide resistance is common, but the combination of sulphamethoxazole+trimethoprim (Co-trimoxazole) is a valuable antimicrobial in certain situations (e.g. Treating Pneumocystis jiroveci pneumonia) * Trimethoprim is used for Rx community-acquired UTIs

Answer 21

``` • Chemical modification or inactivation of the antibiotic • Modification or replacement of target • Reduced antibiotic accumulation 1) Impaired uptake 2)Enhanced efflux • Bypass antibiotic sensitive step ```

Answer 22

1) Inactivation ß Lactams Aminoglycosides Chloramphenicol ``` 2) Altered Target ß Lactams Macrolides Quinolones Rifampicin Chloramphenicol Linezolid Glycopeptides ``` ``` 3)Reduced Accumulation Tetracyclines ß Lactams Aminoglycosides Quinolones Chloramphenicol ``` 4)Bypass Trimethoprim Sulphonamides

Answer 23

* ß Lactamases are a major mechanism of resistance to ß Lactam antibiotics in Staphylococcus aureus and Gram Negative Bacilli (Coliforms). * NOT the mechanism of resistance in penicillin resistant Pneumococci and MRSA. * Penicillin resistance not reported in Group A (S. pyogenes), B, C, or G ß haemolytic Streptococci.

Answer 24

* mecA gene encodes a novel PBP (2a) * Low affinity for binding ß Lactams * Substitutes for the essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotic

Answer 25

* Penicillin resistance is the result of stepwise mutations in PBP genes * Lower level resistance can be overcome by increasing penicillin dose

Answer 26

ESBLs can enzymatically break down cephalosporins (cefotaxime, ceftazidime, cefuroxime) and penicillins but, not carbapenems Flucloxacillin is a member of the penicillin class, but is RESISTANT to beta-lactamase Tazobactam is a beta-lactamase inhibitor which is given along with piperacillin, but which is not itself an antibiotic   More common in E. coli and Klebsiella Treatment failures reported with beta lactam and beta lactamase inhibitor combinations – augmentin/tazocin Aminoglycoside used in combinations   New beta-lactamases are spreading MDR instead of just the ESBL-component of resistance (big problem) If something is erythromycin-resistant, be careful about giving clindamycin (may make the bacteria MDR)

Answer 27

Adenine-N6 methyltransferase modifies 23S rRNA --> reduces binding of MLS antibiotics and results in resistance Encoded by erm (erythromycin ribosome methylation) genes.

Answer 28

* No infection present * Selection of incorrect drug * Inadequate or excessive dose * Inappropriate duration of therapy * Expensive agent used when cheaper is available

Answer 29

* GI upset * Fever & rash * Renal dysfunction * Acute anaphylaxis * Hepatitis

Answer 30

Approximately 5% of hospitalised patients given an antimicrobial experience an adverse event

Answer 31

For patients with non-severe reactions (such as rash) a related antibiotic class may be considered. (e.g. cephalosporins in penicillin allergy)

Answer 32

``` CHOICE of the correct antimicrobial depends upon the HOST characteristics ANTIMICROBIAL susceptibilities of the ORGANISM itself and also the SITE of the infection ```

Answer 33

Pharmacokinetics • Absorption • Distribution • Elimination Route of administration • I.v. for serious infection or if patient not absorbing p.o. • I.v. if need to access deep site or CNS Dosage • Age • Renal/ hepatic function • Drug monitoring

Answer 34

``` Age Allergy Renal function Genetics Hepatic function ```

Answer 35

Use a broad-spectrum agent that is likely to cover the organisms. Collect specimens for culture prior to starting antibiotics The empirical cover may then be changed to a more specific/narrow spectrum agent on the basis of the culture results

Answer 36

* Appropriate initial antibiotic therapy is associated with higher survival rates, shorter hospital stays and lower healthcare costs * Broad spectrum antibiotics are an optimal initial choice for nosocomial pneumonia and severe sepsis

Answer 37

Gram stain: • CSF • Joint aspirate • Pus Rapid antigen detection: • Immunofluorescence • PCR

Answer 38

* pH at the infection site * Lipid-solubility of the drug * Ability to penetrate the blood- brain barrier (CNS infections)

Answer 39

Is there evidence of a systemic response, e.g. •Fever •Raised CRP • High WBC count (neutrophils +++) or very low WBC count ``` Also consider: •Duration of symptoms •Underlying risk factors •Likely source of infection •Exclude other pro-inflammatory medical disease ```

Answer 40

i.v. Serious (or deep-seated) infection p.o. Usually easy, but avoid if poor GI function or vomiting Different classes of antimicrobial have different oral bioavailabilities i.m. Not an option for long-term use Avoid if bleeding tendency or drug is locally irritant Topical Limited application and may cause local sensitisation

Answer 41

N. meningitidis meningitis 7 days ``` Acute osteomyelitis (adult) 6 weeks ``` Bacterial endocarditis 4-6 weeks Gp A Streptococcal pharyngitis 10 days ``` Simple cystitis (in women) 3 days ```

Answer 42

4 million in Europe ~8% May be around 25% in developing nations

Answer 43

~£1 billion a year | 15-30% are preventable

Answer 44

Hospital acquired pneumonia (~25%)

Answer 45

Gram-positive spore-forming anaerobe

Answer 46

In the gut - transmissible and can contaminate environment and persist for long periods of time

Answer 47

– Toxinotype III/BI/NAP1/027 – Pro-inflammatory – causes inflammation – Cytotoxic – cell damage – Enterotoxic – damage to the gut

Answer 48

Mild diarrhoea → severe colitis – dehydration, pseudomembranous colitis, perforation Attack rates higher in – older – debilitated – antibiotic-treated

Answer 49

Fidaxomicin

Answer 50

- Macrocyclic antibiotic | - Non-inferior to vancomycin for response to treatment and lower recurrence

Answer 51

Faecal transfer: microbiome. fresh faeces, healthy donor

Answer 52

Colonised very rapidly - 60% within 96hrs

Answer 53

– Chromosomal – Plasmid-mediated E. coli < Klebsiella < Enterobacter

Answer 54

- Wound environment - Host defence - Pathogens

Answer 55

- Do not remove hair routinely to reduce risk of surgical site infection - Antibiotic prophylaxis - clean surgery involving. placement of prosthesis or implant, clean-contaminated surgery

Answer 56

Staphylococcus aureus

Answer 57

Normally preceded by colonisation Skin breach: skin disease, chronic disease, invasive procedure, device

Answer 58

Improving infection control activities (improving transmission) --> measuring --> analysing (data management) --> feedback and altering practice

Answer 59

Environmental hygiene e.g. C. difficile, Norovirus, Acinetobacter outbreaks Environmental sources Legionella- cooling towers Aspergillus- building works Negative pressure isolation: TB, Chickenpox, RSV

Answer 60

a) Haematogenous spread b) Direct implantation - via instrumentation c) Local extension - secondary to established infections d) PNS into CNS

Answer 61

Meningitis: inflammatory process of meninges and CSF Meningoencephalitis: inflammation of meninges and brain parenchyma

Answer 62

Direct bacterial toxicity Indirect inflammatory process and cytokine release and oedema Shock, seizures, and cerebral hypo-perfusion

Answer 63

``` Neisseria meningitidis Streptococcus pneumoniae Haemophilus influenzae Listeria monocytogenes Group B Streptococcus Escherichia coli ```

Answer 64

Infectious cause of childhood death in all countries. Transmission is person-to-person, from asymptomatic carriers. Pathogenic strains are found in only 1% of carriers. Cause infections in less than 10 days.

Answer 65

A nonblanching rash (petechial or purpuric) develops in 80% of children. A maculopapular rash remains in 13% of children, and no rash occurs in 7%.

Answer 66

1) Capillary leak - albumin and other plasma proteins leads to hypovolaemia 2) Coagulopathy - leads to bleeding and thrombosis 3) Metabolic derangement - particularly acidosis 4) Myocardial failure

Answer 67

CT scan - tuberculous meningitis – enhancement in the basal cistern and meninges, with dilatation of the ventricles

Answer 68

Incidence: 544 per 100,000 population in Africa. More common in patients who are immunosuppressed. Mortality was 5.5 deaths per 100,000 persons. Involves the meninges and basal cisterns of the brain and spinal cord. Can result in tuberculous granulomas, tuberculous abscesses, or cerebritis.

Answer 69

Aseptic meningitis is the most common infection of the CNS. Patients with aseptic meningitis have headache, stiff neck, and photophobia. A nonspecific rash can accompany these symptoms. Enteroviruses (e.g. Coxsackievirus group B and echoviruses) are responsible for 80-90% cases in which a causative organism of aseptic meningitis is identified. It most frequently occurs in children younger than 1 year. The clinical course of aseptic meningitis is self-limited and resolves in 1-2 weeks.

Answer 70

Mosquitoes Lice Ticks Various viridae from Togavirus, Flavivirus, and Bunyavirus families. West Nile virus is becoming the leading cause of encephalitis.

Answer 71

Bacterial encephalitis - Listeria monocytogenes Amoebic encephalitis - Naegleria fowleri - Habitat – warm water - Acanthamoeba species, and Balamuthia mandrillaris, brain abscess, aseptic or chronic meningitis

Answer 72

An obligate intracellular protozoal parasite, Toxoplasma gondii. Via the oral, transplacental route or organ transplantation. Severe infection in immunocompromised patients. Affected organs include the gray and white matter of the brain, retinas, alveolar lining of the lungs, heart and skeletal muscle.

Answer 73

Pathophysiology: otitis media/mastoiditis/paranasal sinuses/endocarditis/haematogenously

Answer 74

Streptococci (both aerobic and anaerobic) Staphylococci, Gram-negative organisms (particularly in neonates) Mycobacterium tuberculosis Fungi Parasites Actinomyces and Nocardia species

Answer 75

``` Advanced age Intravenous drug use Long-term systemic steroids Diabetes mellitus Organ transplantation Malnutrition Cancer ```

Answer 76

MRI is superior to CT scanning in detecting parenchymal abnormalities such as abscesses and infarctions.

Answer 77

MRI oedema pattern and moderate mass effect cannot be differentiated from tumor or stroke or vasculitis in some patients. Infections in early stages and serological tests. Amount of CSF. PCR techniques. Methods to detect amoebic infections. Availability of good laboratory technique.

Answer 78

Ceftriaxone 2g IV bd If >50yrs or immunocompromised add: Amoxicillin 2g iv 4hourly

Answer 79

Aciclovir 10mg/kg iv tds Ceftriaxone 2g iv bd If >50yrs or immunocompromised add: Amoxicillin 2g iv 4hourly

Answer 80

1. Eukaryotic organisms with chitinous cell walls and ergosterol containing plasma membranes 2. Small protein packages containing genetic material; some also contain enzymes 3. Single-celled organisms with prokaryotic cells 4. Single-celled eukaryotes that are either free living or parasitic 5. An organism that lives on or in an organism of another species and benefits by deriving nutrients at the other’s expense

Answer 81

Yeasts – single celled, reproduce by budding | Moulds – multicellular hyphae, grow by branching and extension

Answer 82

Yeasts – single celled, reproduce by budding – Candida – Cryptococcus – Histoplasma (dimorphic) Moulds – multicellular hyphae, grow by branching and extension – Dermatophytes – Aspergillus – Agents of mucormycoses

Answer 83

Candida spp

Answer 84

> 150 Candida spp., but < 10 are human pathogens Clinical manifestations – Acute, subacute, chronic, episodic – Superficial or systemic/invasive

Answer 85

Oral thrush Candida oesophagitis Vulvovaginitis Cutaneous – Localised or generalised

Answer 86

Topical – Oral thrush: nystatin – Vulvovaginitis: cotrimazole – Localised cutaneous: cotrimazole Oral – Vulvovaginitis: fluconazole – Oesophagitis: fluconazole

Answer 87

– Malignancies, esp haematological – Burns patients – Complicated post-op courses (eg Tx or GIT Sx) – Long lines

Answer 88

``` • Look for source and signs of dissemination – Imaging – Serology for beta-D-glucan – ECHO – Fundoscopy ``` • Antifungals for at least 2/52 (from date of first –ve BC) – Echinocandin eg anidulafungin (whilst a/w identification and susceptibilities) * BC every 48 hours * REMOVE ANY LINES/PROSTHETIC MATERIAL

Answer 89

``` • Look for source and signs of dissemination – Imaging – Serology for beta-D-glucan – ECHO – Fundoscopy ``` • Antifungals for at least 2/52 (from date of first –ve BC) – Echinocandin eg anidulafungin (whilst a/w identification and susceptibilities) * BC every 48 hours * REMOVE ANY LINES/PROSTHETIC MATERIAL

Answer 90

``` • Candidaemia • CNS – Dissemination, trauma, Sx • Rx: Ambisome/voriconazole • Endocarditis – Abnormal valves/prosthetic valves, long lines, IVDU • Rx: Ambisome/voriconazole, Sx • Urinary tract – Vulvovaginits, catheters • Rx: Fluconazole • Bone and joint – Dissemination. Trauma • Rx: Ambisome/voriconazle, Sx • Intra-abdominal – Peritoneal dialysis, Sx, perforation • Rx: Echinocandin/Fluconazole ```

Answer 91

• Encapsulated yeast – Serotypes A&D = C neoformans (immunodeficient) – Serotypes B&C = C gattii (immunocompetent) * Transmission by inhalation of aerosolised organisms * Chronic, subacute to acute pulmonary, meningitic or systemic disease

Answer 92

Bird/eucalyptus --> spores --> inhalation --> lodging in alveoli --> dissemination to central nervous system

Answer 93

• Impaired T-cell immunity – E.g patients with HIV, who have reduced CD4 helper T-cell numbers (typically less than 200/ml) • Patients taking T-cell immunosuppressants for solid organ transplant also have a 6% lifetime risk

Answer 94

* Causes a meningitis in apparently immunocompetent individuals in tropical latitudes esp. SE Asia and Australia * High incidence of space-occupying lesions in brain and lung * Increased resistance to amphotericin B clinically

Answer 95

* Typical clinical history/features -Immunosuppressed host * Imaging * India ink staining of CSF * Serum/CSF cryptococcal Ag (CRAG) * Can culture from blood/body fluids

Answer 96

• Induction: – Amphotericin B + flucytosine (at least 2/52) • Consolidation: – High dose fluconazole (at least 8/52) • Maintenance: – Low dose fluconazole (at least 1 year) • Repeat LP for pressure management • Pulmonary disease: – If mild, fluconazole alone

Answer 97

• A mould with worldwide distribution – Mycotoxicosis - ingestion of contaminated foods – Allergy and sequelae - presence of conidia/transient growth of the organism in body orifices – Colonization - in preformed cavities and debilitated tissues – Invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs – Systemic and fatal disseminated disease

Answer 98

* Imaging * Sputum/BAL – MC&S, Ag testing * Aspergillus Abs (precipitans) * Galactomannan * Bx – histology, MC&S

Answer 99

* Voriconazole * Ambisome * Duration based on host/radiological/mycological factors

Answer 100

* Fungal infection which causes pneumonia * Ubiquitous in the environment and distributed worldwide * Lacks ergosterol in it’s cell wall Acquisition by airborne route – Pneumonia – Extrapulmonary disease = rare

Answer 101

– Immunodeficiency – Immunosuppressive drugs – Debilitated infants – Severe proteinnmalnutrition

Answer 102

– Microscopy – PCR – Beta-D-glucan

Answer 103

– High dose cotrimoxazole 2-3/52 – Alternatives: atovaquone, clindamycin + primaquine – Steroids if hypoxia present

Answer 104

It lacks ergosterol in it’s cell wall

Answer 105

* Clinical syndrome caused by a number of fungal species belonging to the order Mucorales eg Rhizopus, Rhizomucor, Mucor * Inoculation via inhalation of spores or primary cutaneous inoculation * Favours immunosuppressed/diabetic patients

Answer 106

• Rhinocerebral => CNS – Cellulitis of the orbit and face progress with discharge of black pus from the palate and nose – Retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness – As the brain is involved, there are decreasing levels of consciousness * Pulmonary * Cutaneous

Answer 107

Isolation from tissue Bx

Answer 108

– Ambisome/Posaconazole – Sx | – Rx guided by response

Answer 109

* A group of fungi capable of invading dead keratin of skin, hair and nails * Classified by site infected e.g tinea capitis * Spread via contact with desquamated skin scales

Answer 110

– Moisture – Deficiencies in cell-mediated immunity – Genetic predisposition

Answer 111

Foot -> tinea pedis Scalp -> tinea capitis Groin -> tinea cruris Abdomen -> tinea corporis

Answer 112

Trichophyton rubrum | Tonsuurans

Answer 113

Trichophyton spp Epidermophyton spp Microsporum spp

Answer 114

Tinea versicolor is skin infection with Malassezia furfur that manifests as multiple asymptomatic hypo pigmented scaly patches

Answer 115

Skin scrapings, nail specimens and plucked hairs

Answer 116

Topical e.g. clotrimazole, ketoconazole Oral e.g. griseofulvin, terbinafine, itraconazole

Answer 117

Azoles --> abnormal LFTs Polyenes --> nephrotoxicity Pyrimidine analogues --> blood disorders Echinocandins --> relatively innocuous

Answer 118

Cell membrane Fungi use principally ergosterol instead of cholesterol DNA Synthesis Some compounds may be selectively activated by fungi, arresting DNA synthesis Cell Wall Unlike mammalian cells, fungi have a cell wall

Answer 119

Polyene antibiotics - Amphotericin B, lipid formulations - Nystatin (topical) Azole antifungals - Ketoconazole - Itraconazole - Fluconazole - Voriconazole - Miconazole, clotrimazole (and other topicals)

Answer 120

• In fungi, the cytochrome P450-enzyme lanosterol 14-a demethylase is responsible for the conversion of lanosterol to ergosterol • Azoles bind to lanosterol 14a-demethylase inhibiting the production of ergosterol – Some cross-reactivity is seen with mammalian cytochrome p450 enzymes * Drug Interactions * Impairment of steroidneogenesis (ketoconazole, itraconazole)

Answer 121

* Polyene antibiotic * Fermentation product of Streptomyces nodusus * Binds sterols in fungal cell membrane * Creates transmembrane channel and electrolyte leakage

Answer 122

Aspergillus terreus | Scedosporium spp

Answer 123

• Most significant delayed toxicity • Renovascular and tubular mechanisms – Vascular-decrease in renal blood flow leading to drop in GFR, azotemia – Tubular-distal tubular ischemia, wasting of potassium, sodium, and magnesium • Enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents

Answer 124

1) Liposomal amphotericin B 2) Amphotericin B colloidal dispersion 3) Amphotericin B lipid complex

Answer 125

Echinocandins - Caspofungin acetate (Cancidas)

Answer 126

* Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase * Loss of cell wall glucan results in osmotic fragility • Spectrum: – Candida species including non-albicans isolates resistant to fluconazole – Aspergillus spp. but not activity against other moulds (Fusarium, Zygomycosis) – No coverage of Cryptococcus neoformans

Answer 127

Pyrimidine analogues | - Flucytosine

Answer 128

``` • Restricted spectrum of activity • Acquired Resistance – result of monotherapy – rapid onset • Due to: – Decreased uptake (permease activity) – Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity) ```

Answer 129

Used in candida and cryptococcosis infections in combination with Ambisome/fluconazole

Answer 130

HIT = 1 -1/R0 | Percentage of fully immune individuals required to stop the spread of disease

Answer 131

T cell response

Answer 132

Whole microorganism destroyed by heat, chemicals, radiation or antibiotics (e.g. Influenza, cholera, polio)

Answer 133

Advantages: • Stable • Constituents clearly defined • Unable to cause the infection ``` Disadvantages • Need several doses • Local reactions common • Adjuvant needed • Shorter lasting immunity ```

Answer 134

Live organisms modified to be less virulent

Answer 135

Measles Mumps Rubella Yellow fever

Answer 136

Inactivated toxic components

Answer 137

Tetanus | Diphtheria

Answer 138

Protein component of the microorganisms or synthetic virus like particles. Lacking viral genetic material and unable to replicate.

Answer 139

Hepatits B | HPV

Answer 140

Poorly immunogenic antigens paired with a protein that is highly immunogenic (adjuvant).

Answer 141

Haemophilus influenzae type B

Answer 142

Pathogens that infect other animals but do not cause disease or cause mild disease in humans

Answer 143

Use a modified virus (e.g. adenovirus) to deliver genetic code for an antigen.

Answer 144

Ebola | Janssen and AZ COVID vaccines

Answer 145

Use DNA/RNA from the pathogen.

Answer 146

Pfizer | Moderna

Answer 147

* No animal reservoir * Antigenically stable pathogen with only one (or small number of) strains * No latent reservoir of infection and no integration of pathogen genetic material into host genome * Vaccine must induce a lasting and effective immune response * High coverage required for very contagious pathogens

Answer 148

* Adenoviral vectored vaccines * VITT * 14.2 per million doses * CLS * Pfizer * Lymphadenopathy * Myocarditis

Answer 149

Hep B HIV Syphilis

Answer 150

‘TORCH’ screen: ``` Toxoplasmosis Other – syphilis; HIV; hepatitis B/C Rubella Cytomegalovirus (CMV) Herpes simplex virus (HSV) ```

Answer 151

May be asymptomatic at birth – 60% but may still go on to suffer long term sequelae Deafness, low IQ, microcephaly ``` 40% symptomatic at birth Choroidoretinitis Microcephaly/hydrocephalus Intracranial calcifications Seizures Hepatosplenomegaly/jaundice ```

Answer 152

Effect on foetus – dependent on time of infection Mechanism – mitotic arrest of cells; angiopathy; growth inhibitor effect Eyes: cataracts; microphthalmia; glaucoma; retinopathy Cardiovascular syndrome: PDA; ASD/VSD Ears: deafness Brain: microcephaly; meningoencephalitis; developmental delay Other: growth retardation; bone disease; hepatosplenomegaly; thrombocytopenia; rash

Answer 153

Definition varies First 4-6 weeks of life If born early (premature) Neonatal period longer and is adjusted for expected birth date

Answer 154

Less maternal IgG NICU care Exposure to microorganisms; colonisation and infection

Answer 155

Group B streptococci E. coli Listeria monocytogenes

Answer 156

Gram positive coccus Catalase negative Beta-haemolytic Lancefield Group B In neonates: Bacteraemia Meningitis Disseminated infection e.g. joint infections

Answer 157

Gram negative rod In neonates: Bacteraemia Meningitis UTI

Answer 158

``` PROM/prem. Labour Fever Foetal distress Meconium staining Previous history ```

Answer 159

``` Birth asphyxia Resp. distress Low BP Acidosis Hypoglycaemia Neutropenia Rash Hepatosplenomegaly Jaundice ```

Answer 160

Supportive management: Ventilation Circulation Nutrition Antibiotics: e.g. benzylpenicillin & gentamicin

Answer 161

``` Coagulase negative Staphylococci (CoNS) Group B streptococci E. coli Listeria monocytogenes S. aureus Enterococcus sp. Gram negatives – Klebsiella spp. /Enterobacter spp. /Pseudomonas aeruginosa/Citrobacter koseri Candida species ```

Answer 162

NICU-Example of antibiotics for late onset sepsis: 1st line: cefotaxime & vancomycin 2nd line: meropenem Community acquired late onset neonatal infections: cefotaxime, amoxicillin +/-gentamicin

Answer 163

Leading cause of morbidity and mortality esp. in <2yrs Gram positive diplococcus – alpha haemolytic streptococcus Meningitis, bacteraemia, pneumonia >90 capsular serotypes Increasing penicillin resistance

Answer 164

<3/12: N. meningitidis; S. pneumoniae; (H. influenzae (Hib) if unvaccinated); GBS; E. coli; Listeria sp. 3/12 - 5 years:N. meningitidis; S. pneumoniae; (Hib if unvaccinated) >6 years: N. meningitidis; S. pneumoniae

Answer 165

Acquired by droplet transmission person to person. Epidemics occur every 3-4 years. Occurs in school age children and young adults. Incubation period 2-3 weeks ``` Many asymptomatic Classically presents: Fever Headache Myalgia Pharyngitis Dry cough ```

Answer 166

Haemolysis IgM antibodies to the I antigen on erythrocyte Cold agglutinins in 60% patients Neurological (1% cases) Encephalitis most common Aseptic meningitis, peripheral neuropathy, transverse myelitis, cerebellar ataxia Aetiology unknown ?antibodies cross react with galactocerebroside Cardiac Polyarthralgia, myalgia, arthritis Otitis media and bullous myringitis

Answer 167

Staph.aureus (MSSA and MRSA) E.coli Pseudomonas aeruginosa

Answer 168

If surgical site is contaminated with > 10 5 microorganisms per gram of tissue, risk of SSI is increased. The dose of contaminating bacteria required to cause infection is much lower if there is foreign material present e.g. silk suture

Answer 169

Superficial incisional- affect skin and subcutaneous tissue Deep incisional- affect fascial and muscle layers Organ/space infection- any part of anatomy other than incision

Answer 170

IV linezolid

Answer 171

Age - linear increase in age ASA score of 3 or more Diabetes – association with post-op hyperglycaemia Malnutrition Low serum albumin Radiotherapy and steroid use Rheumatoid arthiritis - DMARDs for 4 weeks before and 8 weeks post-op Obesity - adipose is poorly vascularised Smoking - nicotine delays primary wound healing

Answer 172

S.aureus is carried in the nares of 20-30%

Answer 173

Incidence is 2-10 cases per 100,000 In patients with RA incidence is 28-38 per 100,000 population. Mortality is 7-15% Morbidity is 50%

Answer 174

Organisms adhere to the synovial membrane, bacterial proliferation in the synovial fluid with generation of host inflammatory response. Joint damage leads to exposure of host derived proteins such as fibronectin to which bacteria adhere

Answer 175

Rheumatoid arthritis, osteoarthritis, crystal induced arthritis Joint prosthesis Intravenous drug abuse Diabetes, chronic renal disease, chronic liver disease Immunosuppression- steroids Trauma- intra-articular injection, penetrating injury

Answer 176

Leucocyte derived proteases and cytokines can lead to cartilage degradation and bone loss. Raised intra-articular pressure can hamper capillary blood flow and lead to cartilage and bone ischaemia and necrosis. Genetic deletion of macrophage –derived cytokines (lymphotoxin α, TNFα, interleukin 1 receptor) reduces host protection in S.aureus sepsis in animal models

Answer 177

S.aureus has receptors such as fibronectin binding protein that recognise selected host proteins. Kingella kingae synovial adherence is via bacterial pili Some strains produce the cytotoxin PVL ( Panton-Valentine Leucocidin) which have been associated with fulminant infections.

Answer 178

``` Staph. aureus 46% Coagulase negative staphylococci 4% Streptococci 22% Streptococcus pyogenes Streptococcus pneumoniae Streptococcus agalactiae Gram negative organisms E.coli Haemophilus influezae Neisseria gonorrhoeae Salmonella Rare- Lyme, brucellosis, mycobacteria, fungi ```

Answer 179

1-2 week history of red, painful, swollen restricted joint Monoarticular in 90% Knee is involved in 50% Patients with rheumatoid arthritis may show more subtle signs of joint infection

Answer 180

Blood culture before antibiotics Synovial fluid aspiration for microscopy and culture ESR, CRP Traditionally a synovial count> 50,000 cells/mm3 used to suggest septic arthritis (Negative culture result does not exclude septic arthritis)

Answer 181

X-rays- soft tissue oedema US - confirm effusion and guide needle aspiration CT - erosive bone change, periarticular soft tissue extension MRI - joint effusion, articular cartilage destruction, abscess, contiguous osteomyelitis

Answer 182

IV Cephalosporin or Flucloxacillin - may need to add vancomycin if at high risk of MRSA (up to 6 weeks) Drainage- arthoscopic washout

Answer 183

Acute haematogenous Exogenous - after disc surgery - implant associated

Answer 184

S.aureus - 48.3% CNS - 6.7% GNR - 23.1% Strep - 43.1%

Answer 185

cervical - 10.6% cervico-thoraco - 0.4% lumbar - 43.1%

Answer 186

Back pain 86% Fever 60% Neurological impairment 34%

Answer 187

Pain Brodies abscess Sinus tract

Answer 188

Radical debridement down to living bone - remove sequestra, and remove infected bone and soft tissue 1) Lautenbach technique 2) Papineau technique (complete excision)

Answer 189

Pain Patient complains that the joint was ‘never right’ Early failure Sinus tract

Answer 190

``` Gram positive cocci -coagulase negative staphylococci -staphylococus aureus Streptococci sp Enterococci sp ``` Aerobic gram negative bacilli Enterobacteriaceae Pseudomonas aeruginosa Anaerobes Polymicrobial Culture negative Fungi

Answer 191

Tissue specimens from at least 5 sites around the implant Histopathology – infection defined as >5 neutrophils per high power field If 3 or more specimens yield identical organisms, this is highly predictive of infection (sensitivity 65%, specificity 99%)

Answer 192

Complicated - UTI + functional or structural abnormality Uncomplicated - infection in structurally and neurologically normal urinary tract

Answer 193

O1, O2, O4, O6, O7, O8, O75, O150, O18ab - different virulence factors

Answer 194

- Proteus mirabilis - Klebsiella aerogenes - Staphylococcus saprophyticus - Staphylococcus epidermis Higher prevalence when there is a structural abnormality

Answer 195

Shorter urethra and more proximity to warm moist vulvar and perianal areas - can colonise the vaginal Introits and the periurethral area

Answer 196

- Extrarenal - valves, stenosis or bands, calculi, BPH | - Intrarenal - nephrocalcinosis, uric acid neophropathy, PKD, hypokalaemia nephropathy, renal lesions of sickle cell

Answer 197

- Poliomyelitis - Tabes dorsaliis - Diabetic neuropathy - Spinal cord injuries

Answer 198

Kidney site of abscesses in patients with staph. aureus (rarely gram negative bacilli)

Answer 199

Under 2: failure to thrive, vomiting, fever Over 2: frequency, dysuria, abdominal or flank pain

Answer 200

Renal USS | IV urography

Answer 201

- MSU - Catheterisation - Suprapubic aspiration

Answer 202

1) White cells pyuria - infection | 2) Squamous epithelial cells - contamination

Answer 203

E.coli - pink | Enterococcus - blue

Answer 204

- Female: cefalexin, nitrofurantoin - Pregnant/breastfeeding female: cefalexin, co-amoxiclav - Male - cefalexin, ciprofloxacin - Pyelonephritis - co-amoxiclav +/-gentamicin (IV) - Catheter-associated: gentamicin, amikacin

Answer 205

Uncomplicated: 3 days Complicated: 7 days

Answer 206

Candida UTIs | Fluconazole treatment

Answer 207

‘Endogenous’ Latent viruses that reactivate in absence of immune system Acquired in past prior to immune suppression e.g. Varicella Zoster ‘Exogenous’ Viruses acquired from environment increased severity in immunosuppressed e.g. Influenza, SARS-CoV-2

Answer 208

Indirect detection: response of the immune system to the virus These tests are useful to see if you have ever had the infection Direct detection: fragments of the actual virus Viral proteins (lateral flow/antigen tests) Viral genetic material (the virus genetic material present with patient sample Polymerase chain reaction

Answer 209

+++ IgM indicate Active or Resolving infection +++ IgG indicates past infection > 6 weeks ago Antibody levels ↓↓↓ reduced in Immunosuppressed

Answer 210

Serological screening - antigens and antibodies for HBV Monitoring/prophylaxis - PCR

Answer 211

Allogeneic stem cell transplant Advanced HIV infection (CD4 dep) Solid organ transplant Various monoclonal antibody therapies Cytotoxic chemotherapy DMARDs and steroids

Answer 212

Increased frequency Increased severity /risk of dissemination More organs can be involved (pneumonitis, eosophagitis, hepatitis); NB: not enceph! Increased risk of acyclovir resistance

Answer 213

HIV/AIDS CD4 <200 ``` Prophylaxis Test for HSV IgG Bone marrow 1 month (until engraftment) Solid organ 3-6 months And if treated for rejection ```

Answer 214

``` Varicella (chicken-pox) Pneumonitis Encephalitis Hepatitis Purpura fulminans in neonate ``` Zoster (shingles) Multi-dermatomal / disseminated Often a late presenting immunosuppression

Answer 215

Prevention: prophylaxis, PEP, vaccination Treatment: Varicella Anti-viral for 7-10 days IV until no new lesions; PO until all crusted Zoster Anti-viral (IV if disseminated) + analgesia If Ramsay-Hunt: add steroids If HZO: add topical steroids

Answer 216

Latently infected B cells – polyclonal activation Predisposes to lymphoma Suspicion on rising EBV viral load (> 105 c/ml) and CT scan Confirmation with biopsy of lymph nodes

Answer 217

Oncogenesis B cell latency, high turn-over T-cells monitor/control this B-cell lymphomas PTLD (post-transplant lympho-proliferative disorder)

Answer 218

Monitor EBV levels Ix for lymphoma as needed Rx: ?Rituximab Rx: reduce immunosuppression

Answer 219

``` HIV/AIDS: CD4 <50 Ocular (retinitis) Polyradiculopathy Pneumonitis GI tract ``` SOT Allograft disease GI tract (i.e. renal)

Answer 220

Prophylaxis (i.e. lung transplant) Pre-emptive treatment (i.e. renal transplant / HSCT) Treat if disease (HIV/AIDS) Rx: Ganciclovir / Valganciclovir ``` Ganciclovir (IV): bone marrow suppression Valganciclovir: oral Foscarnet (IV) (nephrotoxicity) Cidofovir (nephrotoxicity) IVIg (with another drug for pneumonitis) ```

Answer 221

CMV viral load twice weekly, treat if virus reactivates until suppressed (pre-emptive therapy) Valganciclovir prophylaxis for 100 days

Answer 222

JC virus is a polyomavirus Progressive multifocal leukoencephalopathy Effective antiretroviral therapy has drastically reduced PML incidence in HIV+ve patient PML can be seen in other types of immunosuppressed humanised monoclonal antibodies Natalizumab (for treatment of multiple sclerosis)

Answer 223

Cognitive disturbance, personality change, motor deficits other focal neurological signs Demyelination of white matter → neurological deficits Diagnosis: MRI and PCR on CSF

Answer 224

Polyomavirus Double stranded DNA BK cystitis post SCT BK nephropathy post Renal Tx

Answer 225

Increased risk of complications (pneumonitis) and high mortality associated particularly with: Influenza A and B Parainfluenza 1, 2, 3 and 4 Respiratory Syncytial Virus (RSV) Adenovirus SARS-CoV-2 Influenza A and B → Oseltamivir (oral drug) for 5 days Resistance/severe/immunosuppressed → zanamivir (inhalation or IV) SARS-CoV-2 Sotrovimab or Casirivimab/imdevimab

Answer 226

Hep A: more severe, vaccinate Hep B: re-activation, vaccinate/prophylaxis Hep C: ?increased fibrosis, Rx direct-acting antiviral Hep E: chronic infection, reduce immunosuppression

Answer 227

Reactivation ↑ B-cell depleting therapies (i.e Rituximab) IL-6 inhibitor COVID also a risk Prevention: Nucleoside (lamivudine), nucleotide (tenofovir, entecavir) Prophylaxis

Answer 228

Markers of disease: sAg+ Circulating virus cAb+ (IgM) Acute immune response eAg+ Circulating virus Markers of immunity: sAb+ Generated from: sAg (virus) sAg (vaccine) cAb+ (IgG/total) Generated from cAg (virus) Prior infection eAb+ Generated from eAg (virus)

Answer 229

A rapid onset diarrheal illness, lasting less than 2 weeks with diarrhoea (loose and unformed stool) three or more times a day or at least 200 g of stool which is either viral or bacterial in aetiology

Answer 230

Small bowel diarrhea- often watery, associated with crampy abdominal pain and of large volume with bloating and gas. Accompanying fever and blood or inflammatory cells in the stool are rare. Large bowel diarrhea –small volume painful stool which occur often with blood, mucus and inflammatory cells found in the stools and an accompanying fever.

Answer 231

Loose or watery stools passed at least three times in 24 hours which can be acute, chronic or persistent Acute-lasting less than 14 days often due to either viral or bacterial pathogens Persistent- between 14-29 days Chronic- lasting greater than 30 days, may be due to parasites and non-infectious aetiology should be excluded

Answer 232

cAMP: opens Cl channel at apical membrane of enterocytes Efflux of Cl to lumen: loss of H2O and electrolytes

Answer 233

Superantigens bind directly to T-cell receptors and MHC molecules; outside the peptide binding site >> massive cytokine production by CD4 cells ie systemic toxicity and suppression of adaptive response

Answer 234

Host responses in bacteraemia: Inflammatory (exudative) diarrhoea Vs Enteric fever; interstitial inflammation

Answer 235

Aortitis, osteomyelitis, deep tissue infection - Salmonella, Yersinia Haemolytic aneamia - Campylobacter, Yersinia Glomerulonephritis - Shigella, Campylobacter, Yersinia Hemolytic uremic syndrome - STEC, Shigella dysenteriae serotype 1 Erythema nodosum - Yersinia, Campylobacter, Salmonella, Shigella Reactive arthritis - Salmonella, Shigella, Campylobacter, Yersinia, rarely Giardia, and Cyclospora cayetanensis Meningitis - Listeria, Salmonella (infants ≤3 months of age are at high risk)

Answer 236

Staphylococcus aureus 1/3 population chronic carriers, 1/3 transient Spread by skin lesions on food handlers Catalase, coagulase positive Gram positive coccus Appears in tetrads, clusters on Gram stain Golden colonies on blood agar Produces enterotoxin, an exotoxin that can act as a superantigen in the GI tract, releasing IL1 and IL2 --> prominent vomiting and diarrhoea

Answer 237

Bacillus cereus : food poisoning Spores germinate in reheated fried rice Heat labile diarrhoeal toxin - food is not cooked to a high enough temperature Watery non bloody diarrhoea; self limited Rare cause of bacteraemia in vulnerable population Can cause cerebral abscesses

Answer 238

Clostridium botulinum : botulism Source : canned or vacuum packed food (honey / infants) Ingestion of preformed toxin (inactivated by cooking) Blocks Ach release from peripheral nerve synapses Treatment with antitoxin Clostridium pefringens : food poisoning Source : reheated food (meat) Normal flora of colon but not small bowel, where the enterotoxin acts (superantigen) Incubation 8-16hrs Watery diarrhoea, cramps,little vomiting lasting 24hrs Clostiridium difficile : Pseudomembranous colitis

Answer 239

It is not an invasive disease and non-toxin producing strains do not often cause disease but can colonise the gut and asymptomatic shedders of spores can continue to act as a reservoir for infection

Answer 240

C.difficle produces two toxins; Toxin A, an enterotoxin and Toxin B, a cytotoxin Toxin A causes inflammation with intestinal fluid secretion and damage to the mucosa Toxin B, more potent than toxin A acts as a virulence factor 3%, 30% of hospitalised patients Antibiotic related colitis (any but.. mainly cephalosporins, cipro and clindamycin)

Answer 241

Vancomycin | Stop other antibiotics where possible

Answer 242

Outbreaks of febrile gastroenteritis ß haemolytic, aesculin positive with tumbling motility Source : refrigerated food (“cold enhancement”) i.e. unpasteurised dairy, vegetables

Answer 243

Grows at 4 ºC GI watery diarrhoea, cramps, headache, fever, little vomiting Perinatal infection, immunocompromised patients

Answer 244

Amoxicillin

Answer 245

Facultative anaerobes, glucose/lactose fermenters (LF), oxidase negative 1) E.coli: traveller's diarrhoea, faeces, enterotoxins 2) Enteropathogenic E. coli (EPEC) pathogenic, infantile diarrhoea 3) Enteroinvasive E. coli (EIEC) invasive, dysentery 4) Enterohemorrhagic E. coli (EHEC, also called Shiga toxin-producing E. coli or STEC) 5) O157:H7 EHEC: shiga- like verocytotoxin causes HUS AVOID ANTIBIOTICS

Answer 246

- Heat labile stimulates adenyl cyclase and cAMP - Heat stable stimulates guanylate cyclase - Act on the jejeunum, ileum not on colon

Answer 247

Non lactose fermenters, H2S producers, TSI agar, XLD agar, selenite F broth Antigens: - cell wall O (groups A-I) - flagellar H - capsular Vi (virulence, antiphagocytic) Many species : - S. typhi (and paratyphi) - S.enteritidis - S.cholerasuis

Answer 248

Enterocolitis Transmitted from poultry, eggs, meat Invasion of epi- and sub-epithelial, tissue of small and large bowel Bacteraemia infrequent <5% Diarrhea resolves in 4-7 days with abdominal pain Nausea, vomiting and fever resolves in 48 to 72 hours Usually self limiting and does not require treatment for immune-competent patients aged between 12-50 years of age Stool positivity

Answer 249

Typhoid (enteric) fever transmitted only by humans multiplies in Payer’s patches, spreads ERS bacteraemia, 3% carriers Slow onset, fever and constipation, splenomegaly, rose spots, anaemia, leucopaenia, bradycardia, haemorrhage and perforation Blood culture positive 40-80% Stool culture positivity is 30-40% Bone marrow may have additional yield >90% in more complicated cases or if unresponsive to treatment and can remain positive for >5 days after antibiotic initiation

Answer 250

Non lactose fermenters, non H2S producers, non motile Antigens: cell wall O antigens, polysaccharide (groups A-D): S.sonnei, S.dysenteriae, S.flexneri (MSM) The most effective enteric pathogen (low ID 10-100) No animal reservoir No carrier state - Dysentery - Invading cells of mucosa of distal ileum and colon - Producing enterotoxin (Shiga toxin) - Abdominal pain 70-93% and watery diarrhoea 30-40% which proceeds to bloody diarrhoea 35-55% - Fever 30-40% of patients - Vomiting 35% - Disease is self-limiting to about seven days - Antibiotic choice should be based on patient demographics and likely local resistance profile

Answer 251

Curved, comma shaped, late lactose fermenters, oxidase positive 1) Vibrio cholerae (the causative agent of cholera) 2) Vibrio parahaemolyticus 3) Vibrio vulnificus can cause diarrhoea, but has been isolated from the blood and tissues of septic patients (especially those with liver disease)

Answer 252

Doxycycline

Answer 253

1) Vibrio cholerae: O1 group: epidemics, biotypes El Tor, Cholerae and serotypes Ogawa, Inaba, Hikojima Non O1 group: sporadic or non pathogens Transmitted by contamination of water and food from human faeces (shellfish, oysters, shrimp) Colonisation of small bowel and secretion of enterotoxin with A and B subunit, causing persistent stimulation of adenylate cyclase Causes massive diarrhoea (rice water stool) without inflammatory cells Treat the losses 2) Vibrio parahaemolyticus Ingestion of raw or undercooked seafood (ie oysters), Major cause of diarrhoea in Japan..or when cruising in the Carribean.. , Self limited for 3 days Cholerae : grows in salty 8.5% NaCl 3) Vibrio vulnificus Cellulitis in shellfish handlers Fatal septicaemia with D+V in HIV patients

Answer 254

``` Curved, comma or S shaped Microaerophilic C.jejuni at 42 ºC Oxidase pos ,motile Transmitted via contaminated food and water with animal faeces ``` ? Enterotoxin (watery diarrhoea) ? Invasion (+/- blood) Loose stools 10 times a day Self-limiting - TREAT WITH MACROLIDE IF IMMUNOCOMPROMISED (Treat with erythromycin or cipro if in the first 4-5 days) GBS syndrome, reactive arthritis, Reiter’s

Answer 255

- Non lactose fermenter, prefers 4ºC “cold enrichment” - Transmitted via food contaminated with domestic animals excreta - enterocolitis - mesenteric adenitis - associated with reactive arthritis , Reiter’s

Answer 256

- Will appear as Gram variable | - Consider TB

Answer 257

1) Entamoeba histolytica:

Answer 258

1) Entamoeba histolytica 2) Giardia lamblia 3) Cryptosporidium parvum

Answer 259

Motile trophozoite in diarrhoea Non motile cyst in nondiarrhoeal illness Killed by boiling, removed by water filters 4 nuclei No animal reservoir Ileum >> colonize cecum, colon >> “flask shaped” ulcer Chronic : wt loss,+/- diarrhoea Liver abscess

Answer 260

Metronidazole + paromomycin in luminal disease

Answer 261

- Trophozoite “pear shaped” - 2 nuclei - 4 flagellas and a suction disk - Ingestion of cyst from fecally contaminated water, food - Excystation at duodenum tropho attaches - No invasion - Malabsorption of protein and fat --> foul smelling non-bloody diarrhoea, cramps, no fever, flatulence

Answer 262

Diagnosis : stool micro, ELISA, “string test” Treatment :metronidazole

Answer 263

Infects the jejunum Severe diarrhoea in the immunocomromised Oocysts seen in stool by modified Kinyoun acid fast stain Treatment : reconstitution of immune system

Answer 264

``` 1) Norovirus: GII.4 currently predominant strain, faeco-oral route from person to person Low ID (18-1000 viral particles) Environmental resilience (0-60 ºC) No long term immunity Incubation period is 24-48 hours Shedding in the stool as long as 4 weeks/months in immunocompromised ``` ``` 2) Rotavirus dsRNA “wheel like” Symptoms 3-8 days and occurs in children aged 6m-2yrs Occasionally in elderly Often year round in tropical climates and in the winter months in temperate areas Vomiting is less common Replicates in mucosa of small intestine Secretory diarrhoea, no inflammation Watery diarrhoea 6yrs - most have antibodies Natural infection twice = lifelong immunity Economic burden worldwide ``` ``` 3) Adenovirus Types 40, 41 cause non bloody diarrhoea <2yrs of age Any type in immunocompromised Diagnosis: stool EM, antigen detection, PCR Poliovirus Enteroviruses (coxsackie, ECHO) Hepatitis A Transmitted via faecal-oral route ```

Answer 265

``` Cholera: serogroups O1(Inaba , Ogawa, biotypes El Tor and classical), O139 Inactivated, whole cell, contains all above + B subunit of toxin (PO) Live attenuated (PO) not recommended ``` Campylobacter : military, infants, traveller, candidate vaccines exist.. ETEC: inactivated and live vaccines in trials Salmonella typhi: Vi capsular PS (IM) and (PO)live Rotavirus Rotarix : live attenuated human strain monovalent, 2(PO) doses Rotateq : pentavalent, 3 (PO) doses, one bovine and four human strains Rotashield and intussusception (8-20 weeks) Given at 6-12w

Answer 266

1) Campylobacter 2) Clostridium sp 3) Listeria monocytogenes 4) Vibrio 5) Yersinia

Answer 267

- Influenza - SARS-CoV-2 - Nipah - West Nile Virus - Dengue - Zika

Answer 268

ANP32 proteins

Answer 269

Polymerase adaptation to mammals can be achieved by a single amino acid change in PB2 E627K

Answer 270

H1N1 Human Adapted | H2N2 Avian virus

Answer 271

1) Transmission requires incoming virus to penetrate mucus and infect epithelial cells 2) Incompatibility of avian-origin influenza virus with human respiratory tract 3) Avian influenza HA must adapt for transmission in humans by acquiring affinity for human receptors --> Neu5Ac binds to Gal at a2,6 instead of a2,3 - entry is pH sensitive

Answer 272

Influenza A viruses mediate binding to cell surface sialic acid receptors via the haemagglutinin (HA) glycoprotein, with the neuraminidase (NA) glycoprotein being responsible for cleaving the receptor to allow virus release. Blocking it stops viral release.

Answer 273

Oseltamivir (Tamiflu) | Zanamivir (Relenza)

Answer 274

Baloxavir inhibits the PA endonuclease

Answer 275

Inactivated vaccine Split or subunit- HA rich Given to those at risk Short term strain specific immunity mediated by antibody to HA head Live attenuated vaccine Cold adapted virus limited to urt Given to children Broader more cross reactive immunity including cellular response

Answer 276

A nested set of mRNAs from one large genome

Answer 277

SARS and SARS CoV2 bind to cells via ACE 2

Answer 278

Dexamethasone Monoclonal antibodies: Regeneron, Sotrovimab Small molecule antivirals: Molnupiravir: targets polymerase, nucleoside analgue Paxlovid: targets protease

Answer 279

Encode stabilised spike

Answer 280

Picornaviridae, genus hepatovirus Single-stranded, positive sense RNA genome Quasi-enveloped virions Faeco-oral versus blood-borne transmission Incubation period of 15-50 days

Answer 281

Acute infection: IgM reactive; unlikely if bilirubin level <30umol/L Past infection: IgM nonreactive, IgG reactive

Answer 282

Two weeks before onset of first symptoms and until one week after the onset of jaundice

Answer 283

The family Hepadnaviridae Double-strained DNA with reverse transcriptase Enveloped virions 10 genotypes (A-J) with distinctive geographic distribution Blood-borne transmission: horizontal & vertical Incubation period of 40-160 days

Answer 284

HBeAg as the most important risk predictor for vertical transmission

Answer 285

Persistence of HBsAg for 6 months or more after acute HBV infection

Answer 286

- Cirrhosis: 8-20% untreated CHB in 5 years; - Hepatocellular carcinoma: the annual risk of 2-5% among CHB cirrhotic patients; affected by host (e.g. alcohol abuse) and viral factors (e.g. high HBV viral load & qHBsAg)

Answer 287

``` HBsAg: infection HBsAb: immunity through either immunisation or past infection HBcAb: exposure IgM: acute infection HbeAg: replication activity HBeAB ```

Answer 288

Single-stranded, circular RNA genome A defective virus that relies on HBV for propagation Blood-borne transmission Incubation period: 3-6 weeks

Answer 289

The family Flaviviridae, genus Hepacivirus Single-stranded, positive sense RNA genome Blood borne transmission Incubation period: 2-6 weeks

Answer 290

Revolutionised the treatment for acute/chronic HCV infection Any HCV cases should be considered 8 or 12 weeks Sustained virological response (SVR) at week 12 Pan-genotypic regimen Single-tablet regimen Drug-drug interaction

Answer 291

The family Hepeviridae, genus Orthohepevirus; species A strains (8 genotypoes) infect humans G1 & G2: obligate human pathogens G3 & G4: zoonotic; pigs & wild boar are natural hosts Single-stranded, positive sense RNA genome Quasi-enveloped HEV Faeco-oral versus blood-borne transmission Incubation period: 15-60 days

Answer 292

- Reverse transcription - Transcription and translation - Release (cell lysis)

Answer 293

1) Alpha: HSV-1, HSV-2, VZV 2) Beta: CMV, HHV-6, HHV-7 3) Gamma: EBV, HHV-8

Answer 294

Alpha: rapid growth, latency in sensory ganglia Beta: slow growth restricted host range Gamma: oncogenic

Answer 295

Immunocompetent: dermatomal distribution, post-herpetic neuralgia Immunocompromised: multidermatomal or disseminated infection

Answer 296

A prodrug is an inactive precursor of a drug, that is metabolized into the active form within the body.

Answer 297

1st line: 1) Aciclovir (po/iv) 2) Valaciclovir (prodrug of acyclovir - high bioavailability) 2nd line: 1) Famciclovir: Foscarnet or cidofovir for ACV-resistant virus 2) Ganciclovir Interfere with viral DNA synthesis

Answer 298

Elongation of the DNA chain is impossible because acyclovir lacks the 3' hydroxyl group necessary for the insertion of an additional nucleotide

Answer 299

- Monophosphorylated by viral thymidine kinase (TK) and then further phosphorylation by cellular kinases to ACV-PPP (active form) - Affinity for herpesvirus DNA polymerase is 10- to 30-fold higher than for cellular (host) DNA polymerase for ACV-PPP - Selective activity means reduced drug toxicity - Susceptibility: HSV-1 > HSV-2 >> VZV - VZV 10x less sensitive so higher doses required

Answer 300

On clinical suspicion: Start empiric treatment immediately with iv ACV 10mg/kg tds without waiting for test results If confirmed, treat for 14 - 21 days

Answer 301

Blood monocytes and dendritic cells

Answer 302

- Ganciclovir - Valganciclovir - Foscarnet - Cidofovir - Letermovir

Answer 303

CMV disease in immunocompromised

Answer 304

Ganciclovir and IVIG

Answer 305

- Bone marrow toxicity (leukopenia, thrombocytopenia, anaemia, pancytopenia) - Renal and hepatic toxicity - Bone marrow suppression: neutropenia

Answer 306

Non-competitive inhibitor of viral DNA polymerase Indications: CMV, HSV, (some activity against VZV, EBV, HHV6)

Answer 307

Nephrotoxic

Answer 308

Nucleotide (cytidine) analogue - competitive inhibitor of viral DNA synthesis Indications: third line CMV in immunocompromised

Answer 309

Require hydration and probenicid

Answer 310

``` Effective in vitro against CMV and EBV Directly inhibits viral kinase (UL97) Effective in vitro against GCV-resistant CMV strains Relatively well tolerated Mainly GI side effects ```

Answer 311

CMV DNA terminase inhibitor Remains active against GCV-resistant strains Mainly GI side effects Drug interactions with immunosuppressants (eg cyclosporine, tacrolimus, sirolimus) - need to monitor drug levels of the above

Answer 312

Salivary transmission, infection common in childhood, usually minimally symptomatic and self-limiting Classical cause of infectious mononucleosis Lifelong infection - continuous low grade viral replication in B lymphocytes kept in check by cellular immune system (immunosurveillance) Associated with lymphoproliferative disease in the immunocompromised

Answer 313

EBV | Breakdown of immunosurveillance --> latently infected B cells --> polyclonal expansion

Answer 314

EBV viral load in blood (>105 c/ml), biopsy

Answer 315

Reduce immunosuppression (regression in < 50%) Anti-CD20 monoclonal Ab therapy (B cell marker) – rituximab

Answer 316

Neuraminidase inhibitor | H275Y mutation --> avoid use with oseltamivir resistance

Answer 317

Inhibitor of endonuclease activity of the RNA polymerase complex required for viral gene transcription

Answer 318

Diarrhoea | Bronchitis

Answer 319

- Favipravir: a viral RNA polymerase inhibitor prodrug | - Oseltamivir

Answer 320

Guanosine analogue Inhibits viral RNA synthesis Clinical efficacy for RSV is unclear

Answer 321

Monoclonal antibody against RSV Indication: prevention of serious lower respiratory tract disease caused by RSV in infants

Answer 322

Extended half life mAb | Requires single IM injection to provide protection for the whole winter

Answer 323

- Remdesevir: broad spectrum adenosine nucleotide prodrug. iv. - Molnupiravir: broad spectrum induces viral RNA mutagenesis - Paxlovid: protease inhibitor nirmatrelvir (administered together with low dose ritonavir to increase drug t1/2)

Answer 324

- Ronapreve | - Sotrovimab

Answer 325

Tocilizumab: IL-6 receptor antagonist Sarilumab: IL-6 receptor antagonist Anakinra: IL-1 receptor antagonist

Answer 326

Part of Polyomavirus family (related to JC virus) Primary BK virus infection in childhood with minimal symptoms, but subsequent lifelong carriage in kidneys and urinary tract - BMT - haemorrhagic cystitis - Renal transplant - BK nephritis, ureteric stenosis

Answer 327

Brincidofovir 100mg twice a week Less toxicity – mainly diarrhoea and mild transaminitis Not licensed in UK Main potential is for treatment of adenovirus and of BK virus disease in the immunocompromised

Answer 328

Mutations usually in viral thymidine kinase (95%), and rarely in the viral DNA polymerase (5%)

Answer 329

CMV genetic mutations: In protein kinase gene (UL97) - most common In the DNA polymerase gene (UL54) – rare UL56 terminase gene (letermovir) 2nd line: foscarnet or cidofovir

Answer 330

``` Gram +ve Streptococcus 30-50% of CAP Acute onset Severe pneumonia Fever, rigors Lobar consolidation Almost always penicillin sensitive ```

Answer 331

``` Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Staphylococcus aureus Klebsiella pneumoniae ```

Answer 332

0-1 mths- E.coli, GBS, Listeria 1-6mths- Chlamydia trachomatis, S. aureus, RSV 6mths-5yrs- Mycoplasma, Influenza 16-30yrs-M pneumoniae, S. pneumoniae

Answer 333

``` Typical 85% S. pneumoniae H. influenzae Atypical 15% Legionella Mycoplasma- epidemics 4-6 yrs Coxiella burnetii (Q fever)-worldwide, farm animals, hepatitis Chlamydia psittaci (Psittacosis)-exposure to birds, splenomegaly, rash, haemolytic anaemia ```

Answer 334

``` CURB-65 score Confusion Urea >7 mmol/l RR >30 BP <90 systolic <60 diastolic >65 years ``` Score 2 = consider admitting Score 2-5 = manage as severe

Answer 335

Gram negative cocco-baccelli

Answer 336

More common with pre-existing lung disease | May produce β-lactamase

Answer 337

``` Inhalation of infected water droplets Environmental outbreaks Associated with confusion, abdo pain, diarrhoea Lymphopenia, hyponatremia Dx by antigen in urine/serum Sensitive to macrolides Can cause multi-organ failure Requires special culture: buffered charcoal yeast extract ```

Answer 338

Pneumonia caused by organisms without a cell wall Mycoplasma Legionella Chlamydia Coxiella Cell-wall active antibiotics e.g. penicillins don't work Need agents that work on protein synthesis Macrolides (clarithromycin / erythromycin) Tetracyclines (doxycycline) Extrapulmonary features – e.g. hepatitis; low sodium

Answer 339

Macrolides

Answer 340

Classically upper lobe cavitation (Auramine stain + ZN staiin)

Answer 341

``` Staphylococcus aureus 19% Enterobacteriales 31% Pseudomonas spp 17% Acinetobacter baumannii 6% Fungi (Candida sp.) 7% ```

Answer 342

``` Protozoan Ubiquitous in environment Insidious onset Dry cough, weight loss, SOB, malaise CXR “bat’s wing” Dx Immunofluorescence on BAL Rx Septrin (Co-trimoxazole) Prophylaxis Septrin ```

Answer 343

``` Allergic bronchopulmonary aspergillosis Chronic wheeze, eosinophilia Bronchiectasis Aspergilloma Fungal ball often in pre-existing cavity May cause haemoptysis Invasive aspergillosis Immunocompromised Rx Amphotericin B ```

Answer 344

S. pneumoniae Legionella pneumophila (In severe CAP)

Answer 345

Chlamydia | Legionella

Answer 346

Mild-moderate: Amoxicillin Or erthromycin / clarithromycin Moderate-severe: Needing hospital admission: co-amoxiclav AND clarithromycin Allergic: Cefuroxime AND clarithromycin

Answer 347

First line: Ceftazidime/Ciprofloxacin +/- vancomycin Second line/ITU: Piperacillin/tazobactam AND vancomycin Specific therapy: MRSA: Vancomycin. Pseudomonas: Piperacillin/tazobactam or Ciprofloxacin +/- gentamicin