Micro - Management, Hepatitis Serology, CNS Infections and Congenital/Childhood Infections Flashcards

Question

Rx - varicella zoster

Answer 1

Acyclovir Indications for Rx: - Chickenpox in adults (risk of complication: pneumonitis) - Zoster in adults >50 (risk of complication: post-herpetic neuralgia) - 1o infection or reactivation in the immunocompromised - Neonatal chickenpox - If there is an increased risk of complications

Answer 2

Ganciclovir (IV or vGCV = oral prodrug) Guanosine analogue - inhibits viral DNA synthesis. Primary infection: - Latency in blood monocytes and dendritic cells - Reactivation (eg following immunosuppression) Asymptomatic shedding in saliva, urine, semen and cervical secretions. MAJOR pathogen in the immunocompromised (including solid organ and bone marrow transplant patients) – causes marrow suppression, retinitis, pneumonitis, hepatitis, colitis, encephalitis… Can give: Ganciclovir(GCV) iv. SEs: bone marrow, renal and hepatic toxicity. Contraindicated in BM suppression (neutropenia). Valganciclovir (VGC) po Foscarnet (FOS) iv / intravitreal - Non-competitive inhibitor of viral DNA, polymerase. Use when GCV contraindicated ie neutropenic patients (eg pre-engraftment post-BMT); GCV-resistant CMV; CMV retinitis (intravitreal implants). Nephrotixic. Cidofovir (CDV) iv - Nucleotide (cytidine) analogue (Competitive inhibitor of viral DNA synthesis). Nephrotoxic - Require hydration + probenicid. ``` Also maribavir (inhibits viral kinase (UL97), effective in vitro against GCV resistant CMV), letermovir (CMV DNA terminase* inhibitor) - CMV prophylaxis in CMV+ SCT recipients. Give Ganiciclovir with IVIG for CMV pneumonitis ```

Answer 3

Rituximab (anti-CD20) for post-transplant lymphoproliferative disease (reactivation of EBV with immunosuppression)

Answer 4

Oseltamivir (“Tamiflu”) Neuraminidase inhibitor Inpatients: Indicated for all patients admitted to hospital due to influenza virus-related respiratory disease Indicated in the community if all 3 apply (NICE guidance): - National surveillance indicates influenza is circulating - Patient is in a ‘risk-group’ * - Within 48 hours of symptom onset (36 hours for zanamivir) Peramivir - Neuraminidase inhibitor licensed in US, but also available in UK. H275Y mutation confers reduced susceptibility --> avoid use with oseltamivir resistance Baloxavir merboxil

Answer 5

Treat: ribavirin (Guanosine analogue, PO) Prevent: palivizumab

Answer 6

Herd Immunity threshold = 1 – 1/R0 R0= the average number of people that one sick person will infect. To eliminate a disease the effective R0 needs to be <1. Herd immunity threshold = percentage of fully immune individuals required to stop the spread of disease.

Answer 7

Stimulates all aspects of the immune system e.g. MMR, yellow fever T cell response important in destroying infected cells. Advantages: Single dose often sufficient to induce long-lasting immunity May stimulate response to multiple protective antigens Strong immune response evoked Local and systemic immunity produced – particularly important for infections where CMI plays an important role. Activation of all components of immune system Disadvantages Potential to revert to virulence Can cause illness directly Contraindicated in immunosuppressed patients Interference by viruses or vaccines and passive antibody Poor stability Potential for contamination

Answer 8

Need adjuvant to boost immune response e.g. influenza, polio Whole microorganism destroyed by heat, chemicals, radiation or antibiotics (e.g. Influenza, cholera, polio) Advantages: Stable Constituents clearly defined Unable to cause the infection ``` Disadvantages: Need several doses Local reactions commn Adjuvant needed Shorter lasting immunity ```

Answer 9

Need adjuvant to boost immune response e.g. Hep B, HPV Protein component of the microorganisms or synthetic virus like particles. Lacking viral genetic material and unable to replicate.

Answer 10

Type of cloning --> grow viral proteins which induce immune response

Answer 11

Type of cloning --> inject genes encoding viral antigens --> host cells make the antigens (and therefore induce B and T cells)

Answer 12

Type of cloning --> virus which doe snot replicate (so you can give the intact virus)

Answer 13

Inactivated toxin e.g. tetanus, diptheria

Answer 14

Poorly immunogenic antigens and highly immunogenic adjuvant e.g. haemophilius influenza type B

Answer 15

Pathogens which do not cause disease in humans e.g. BCG

Answer 16

Faecal-oral Acute, never chronic “Fever, malaise, raised ALT in someone coming from India”

Answer 17

DNA virus, same transmission modes as HIV (more likely sex than C) Presents like Hep A, but can cause liver cancer and cirrhosis Treatment: interferon-a and tenofovir

Answer 18

RNA virus, same transmission modes as HIV (more likely blood than B) (“transfusion long time ago”) 80% become chronic --> 25% cirrhosis PCR shows HCV RNA = acute; anti-HCV antibodies = chronic Treatment: antiviral combination

Answer 19

Need Hep B to get Hep D! | Treatment: interferon-a

Answer 20

Like Hep A, but from Indochina, can be chronic and spread via pigs! Treatment: ribavirin

Answer 21

- Surface antigen (HBsAg): current infection (Hep B vaccine is literally just surface antigen) - “e” antigen (HBeAg): high infectivity - Core antibody (anti-HBc): previous infection IgM core antibody: acute IgG core antibody: chronic Surface antibody (anti-HBs): immune Core and surface antibody: immune due to infection Only surface antibody: immune due to vaccination e antibody (anti-HBe): previous acute phase reaction, when virus replicated lots – not as important

Answer 22

Surface antigen = current infection | Core antibody = previous infection

Answer 23

e antigen = infectivity | Hep B DNA = viral load

Answer 24

Acute - bacterial Chronic - TB, cryptococcus (immunocomp) Aseptic - viral (most common, often preceding flu)

Answer 25

Non-blanching rash

Answer 26

Biphasic = young and old

Answer 27

“Tumbling motility” | In eggs/cheese/mayo

Answer 28

Neonatal meningitis

Answer 29

India ink stain (circles are yeast) | = cryptococcus

Answer 30

Ceftriaxone - 2g IV bd If >50y/o or immunocompromised add amoxicillin 2g IV 4 hourly (covers listeria)

Answer 31

Acyclovir 10mg/kg IV tds (covers herpes) Ceftriaxone 2g IV bd If >50y/o or immunocompromised add amoxicillin 2g IV 4 hourly (covers listeria)

Answer 32

- Inactivate the enzymes that are involved in the terminal stages of cell wall synthesis (transpeptidases also known as penicillin binding proteins) – β-lactam is a structural analogue of the enzyme substrate - Bactericidal - Active against rapidly-dividing bacteria - Ineffective against bacteria that lack peptidoglycan cell walls (e.g. Mycoplasma or Chlamydia) Active against rapidly dividing bacteria. Inhibit new cell synthesis --> weak daughter cells --> osmotic lysis. Do not damage the walls of the original cells. No activity if cells aren’t dividing.

Answer 33

Gram positive organisms, Streptococci, Clostridia; broken down by an enzyme (β-lactamase) produced by S. aureus

Answer 34

Relatively non-toxic Renally excreted (so ↓dose if renal impairment) Short half life- most prescribed multiple times per day (need to maintain level in blood for bacterial death) Will not cross intact blood-brain barrier (will cross inflamed meninges, good for meningitis) Cross-allergenic (penicillins approx 10% cross-reactivity with cephalosporins or carbapenems)

Answer 35

used more now due to the rise of resistance - can be used for CAP, meningitis when allergic to cephalasporins - Bacteriostatic - Very broad antibacterial activity - Rarely used (apart from eye preparations and special indications) because 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 36

Bind to amino-acyl site of the 30S ribosomal subunit - prevent elongation of the polypeptide chain --> cause misreading of the codons along the mRNA

Answer 37

Stops formation of peptide cross links and glycocidic bonds --> weakened cell wall --> cells then lyse. Inhibits cell division.

Answer 38

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

Answer 39

Bind to the 50s subunit of the ribosome --> interfere with translocation --> stimulate dissociation of peptidyl-tRNA In v severe cellulitis or necrotizing fasciitis Clarthromycin prevents protein synthesis and so release of bacterial toxins.

Answer 40

Chloramphenicol binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation

Answer 41

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 42

e.g. Ciprofloxacin, Levofloxacin, Moxifloxacin Act on a-subunit of DNA gyrase predominantly, but, together with other antibacterial actions, are essentially bactericidal Broad antibacterial activity, especially vs Gram –ve organisms, including Pseudomonas aeruginosa Newer agents (e.g. levofloxacin, moxifloxacin) increased activity vs G +ves (pneumococcus) and intracellular bacteria, e.g. Chlamydia spp Well absorbed following oral administration Use for UTIs, pneumonia, atypical pneumonia & bacterial gastroenteritis. Be wary of use in unstable pts - hypotensive, tachycardic etc. 25% e colis now resistant to them, almost all salmonella typhi resistant. Big problems with causing c diff infection and tendonitis.

Answer 43

e.g. rifampicin & rifabutin Inhibitors of RNA synthesis.

Answer 44

- 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 Except for short-term prophylaxis (vs. meningococcol 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 45

Cell membrane toxin Cyclic lipopeptide with activity limited to G+ve pathogens. It is a recently-licenced antibiotic likely to be used for treating MRSA and VRE infections as an alternative to linezolid and Synercid.

Answer 46

Cell Membrane Toxin 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. Attacks outer membrane so can allow other abxs to get in.

Answer 47

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 48

Inactivation Altered Target Reduced Accumulation Bypass

Answer 49

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 50

Methicillin Resistant Staphylococcus aureus (MRSA). (also fluclox resistant) 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 51

Penicillin resistance is the result of the acquisition of a series of stepwise mutations in PBP genes. Lower level resistance can be overcome by increasing the dose of penicillin used.

Answer 52

Able to break down cephalosporins (cefotaxime, ceftazidime, cefuroxime) - enzymatic breakdown Becoming more common in E. coli and Klebsiella species. Treatment failures reported with ß Lactam/ ß Lactamase inhibitor combinations (eg. Augmentin/Tazocin).

Answer 53

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

Answer 54

CHAOS ``` CHOICE of the correct antimicrobial depends upon the HOST characteristics ANTIMICROBIAL susceptibilities of the ORGANISM itself and also the SITE of the infection ``` - Ideally narrow spectrum - Ideally bactericidal (vs static) - Ideally choice should be based upon a bacteriological diagnosis (otherwise, “best guess” based upon likely differential diagnosis) - Local sensitivities - Pt characteristics - Cost

Answer 55

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

Answer 56

Sensitivity (based on agar disc diffusion methods)

Answer 57

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

Answer 58

i.v. to p.o. switch is recommended in hospital for most infections if the patient has stabilised after 48 hours i.v. therapy

Answer 59

paradoxically reduced antibacterial effect of penicillin at high doses, though recent usage generally refers to the relative lack of efficacy of beta-lactam antibacterial drugs on infections having large numbers of bacteria. Penicillin is a bactericidal antibiotic that works by inhibiting cell wall synthesis but this synthesis only occurs when bacteria are actively replicating (or in the log phase of growth). In cases of extremely high bacterial burden (such as with Group A Strep), bacteria may be in the stationary phase of growth. In this instance since no bacteria are actively replicating (presumably due to nutrient restriction) penicillin has no activity.

Answer 60

Fluclox Pen allergic - doxy MRSA - Vanc

Answer 61

10 days benpen

Answer 62

Amoxicillin

Answer 63

Co-amox and clarithromycin

Answer 64

cephalosporin; ciprofloxacin; piperacillin/tazobactam If MRSA colonised/risk, consider addition of Vancomycin Second most common cause of HAI. Associated with highest mortality (23%). Greatest risk associated with tracheal intubation and mechanical ventilation.

Answer 65

Ceftriaxone (+/- amoxycillin if Listeria likely) Main pathogens: N. Meningitidis S. pneumoniae +/- Listeria in the very young/elderly/immuno-compromised Baby < 3 months : Cefotaxime PLUS Amoxicillin (to cover for listeriosis) Note: Ceftriaxone not used in neonates as displaces bilirubin from albumin and because it can cause biliary sludging. Neisseria meningitidis: Benzylpenicillin (high dose) or Ceftriaxone/Cefotaxime

Answer 66

- The mechanism of relative resistance to penicillin involves, at least in part, the production of altered forms of one of the penicillin-binding proteins. - Although treatment with penicillin is still effective against these relatively resistant strains, there is evidence that low-dose treatment regimens can fail. - Beta-Lactamase production in meningococci is extremely rare but has been reported

Answer 67

3 days trimethoprim Hospital acquired UTI - cephalexin/augmentin Infected urinary catheter: change under gentamicin cover.

Answer 68

STOP the offending antibiotic (usually a cephalosporin); If severe, Rx with p.o. metronidazole; If above fails, use p.o. vancomycin

Answer 69

- Does the patient really have a bacterial infection? (Have I collected the relevant cultures?) - Is there a persistent focus present (e.g. an infected vascular or urinary catheter)? - Is there a deep-seated collection (e.g. intra-abdominal) that requires drainage? - Could the patient have bacterial endocarditis? - Am I using the correct dose of the antimicrobial? - Is another infection present (esp consider Candida)?

Answer 70

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 71

Achieve and sustain ≥ 95% coverage with two doses of MMR vaccine in the routine childhood programme (<5 years old) Achieve ≥ 95% coverage with two doses of MMR vaccine in older age cohorts through opportunistic and targeted catch-up (>5 years old) Strengthen measles and rubella surveillance through rigorous case investigation and testing ≥80% of all suspected cases with an Oral Fluid Test(OFT) Ensure easy access to high-quality, evidence-based information for health professionals and the public.

Answer 72

Viruses encode specific proteins required for cell entry, genomic replication or transcription, assembly and release of progeny virions: Virally-encoded proteins, e.g. nucleic acid polymerases, proteases, integrase, CCR5, terminase Small molecule inhibitors - directly-acting antivirals (DAAs) - can block production or action of the above and inhibit viral replication

Answer 73

exogenous immunomodulators ``` Examples: Interferon Rx for HBV and HCV IVIG for viral pneumonitis imiquimod for HPV steroids for HSE (?) ```

Answer 74

Chicken pox pneumonitis | Shingles- post-herpetic neuralgia

Answer 75

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

Answer 76

Guanosine analogue Further elongation of the chain is impossible because acyclovir lacks the 3' hydroxyl group necessary for the insertion of an additional nucleotide Selective activity of guanosine analogues: - Monophosphorylated by viral thymidine kinase (TK) - 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 - VZV 10x less sensitive (than HSV) so higher doses required

Answer 77

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 Only becomes problematic in the immunocompromised: - BMT: Haemorrhagic cystitis. Less commonly nephritis. - Renal transplant: BK nephritis and ureteric stenosis Rx: Bladder washouts Reduce level of immunosuppression if possible Cidofovir iv (+ probenicid) if significant morbidity Intravesical cidofovir (5mg/kg/wk) an option if nephrotoxicity Nephropathy - reduce level of immunosuppression, IVIG Brincidofovir - oral prodrug of cidofovir but not licensed in UK

Answer 78

Interferon (combined antiviral and immunomodulatory effects): INF-a Peg-INF a2-a ``` Nucleoside/nucelotide analogues (direct antiviral effect): Tenofovir Telbivudine Entecavir Lamivudine ```

Answer 79

Combination of protease inhibitors, NS5A inhibitors and polymerase inhibitors (nucleoside and non-nucleoside) Can use different DAAs spending on the HCV genotype. glecaprevir/pibrentasvir (Maviret) sofosbuvir/velpatasvir/voxaliprevir (Sovesi) elbasvir/grazoprevir (Zepatier)

Answer 80

Diversity - Quasispecies, mutation / recombination Selection - Replication (eg in the presence of suboptimal drug concentrations)

Answer 81

Treatment failure Change to second line drugs - more toxic Cross resistance (to prevent: Use potent drug regimens to achieve maximal suppression e.g. combo Rx/HAART, increase adherence to Rx)

Answer 82

Genotypic: Sequencing / resistance mutations Example: HIV drug resistance Phenotypic: Cell culture Plaque reduction assay Routinely used for HSV drug resistance testing

Answer 83

Mutations usually in viral thymidine kinase (95%), and rarely in the viral DNA polymerase (5%) The former mediates cross-resistance to GCV Resistance strains selected out by drug treatment Nearly always occurs in the context of immunosuppression – TK-deficient strains less virulent Suspect if lesions fail to resolve despite adequate antiviral therapy Diagnose with viral culture and phenotypic resistance test (plaque reduction assay) – time consuming and requires viable virus to be isolated Treat ACV-resistant HSV with FOS or CDV Virus tends to revert to wild type upon cessation of

Answer 84

CMV genetic mutations: - In protein kinase gene (UL97) - most common - In the DNA polymerase gene (UL54) – rare - UL56 terminase gene (letermovir) Most likely to occur in context of prolonged therapy in immunocompromised Suspect if clinical or virological failure despite appropriate therapy and reduction of immune suppression 2nd line for CMV is foscarnet or cidofovir

Answer 85

Prophylactic: - palivizumab (RSV) Post-exposure prophylaxis: - Varicella zoster immunoglobulin - Immunocompromised / pregnant / neonates - Hepatitis B immunoglobulin - Unvaccinated recipient exposed to hepatitis B-positive source; Non-responder to vaccine exposed to source of positive or unknown status - Human Rabies Immunoglobulin (HRIG) Therapeutic: - Human normal immunoglobulin (IVIG) as adjunctive treatment for viral pneumonitis (eg CMV) - Rituximab (anti-CD20) for EBV-driven PTLD

Micro - Management, Hepatitis Serology, CNS Infections and Congenital/Childhood Infections Flashcards

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