ID Flashcards

Question

Candida and cancer

Answer 1

Cancer | Solid cancer > haematological > post transplant

Answer 2

- Widespread fluconazole use - Prolonged fluconazole prophylaxis - Institutional level Candida forms BIOFILMS

Answer 3

MOA: inhibition of C-14a demethylase (inhibit the cytochrome P450 enzyme ianosterol 14 demethylase) which is required for ergosterol synthesis. Inhibit the cytochrome P450 enzyme lanosterol 14 demethylase resulting in decreased ergosterol production affecting the cell membrane • Fluconazole (mainly used) ○ High oral bioavailability ○ Candidaemia in non-neutropaenic pateints, sensitive Candida ○ Prophylaxis in SCT (stem cell transplant) - high index of suspicion of organism that will be resistant to fluconazole • Itraconazole ○ Broader spectrum ○ Issues with oral absorption ○ GI side-effects and drug-drug interactions • Voriconazole (mainly used) ○ Addition of methyl group to fluconazole backbone ○ Broader coverage including to fluconazole resistant Candida ○ Drug-drug interactions, deranged LFTs (up to 30%), visual side effects, photosensitivity, porphyria, skin cancer, alopecia, petrosis ○ Therapeutic drug monitoring • Posaconazole ○ Increasingly used for prophylaxis and good for resistant organisms

Answer 4

Voriconazole ○ Addition of methyl group to fluconazole backbone ○ Broader coverage including to fluconazole resistant Candida ○ Drug-drug interactions, deranged LFTs (up to 30%), visual side effects, photosensitivity

Answer 5

MOA: Binds to ergosterol in cell MEMBRANE to INCREASED MEMBRANE PERMEABILITY and lead to PORE formation. K channel activity increases with loss of intracellular K Indication: aspergillus, Cryptococcus, mucormycosis • Conventional AmB - significant NEPHROTOXICITY - decreased GFR, direct vasoconstriction of afferent arterioles, K/Mg/HCO wasting - infusion related side effects (fevers, chills, rigors, hypotension, bronchospasm, myalgias, arthralgias, nausea, vomiting & tachycardia) • Liposomal AmB - Unilamellar liposome of 55-75nm diameter containing 1 molecule of amphotericin B per 9 molecules of lipid. - liposome binds preferentially to the fungal cell wall and the amphotericin B is released to bind to ergosterols in the cell membrane → forming pores - Less nephrotoxicity and infusion reaction - Better CSF penetration For treatment of RESISTANT candidaemia

Answer 6

MOA: inhibits synthesis of B-1,3-D-glucan where it inhibits fungal CELL WALL synthesis - Fungicidal against Candida, disrupt growing cell wall of Aspergillus - 97% protein bound - Metabolised slowly by hydrolysis and N-acetylation - Loading dose IV 75mg followed by 50mg daily - No dose adjustment for age/sex/renal function - adjust for severe liver failure - Drug interactions: cyclosporin, Tacrolimus, anteroretroviral agents, phenytoin carbamazepine, rifampicin - Broad septrum of action: NOT C.parapsilosis Indications: treatment of candidaemia in neutropenic or unstable patients, resistant candida

Answer 7

ASID Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections • Neutropaenic Patient: Caspofungin (B1), liposomal Amphotericin B (A11) 3 mg/kg/day. ○ If the organism is a non-albicans Candida species higher doses may be required • Not neutropaenic and fluconazole-sensitive organism: Fluconazole 400 mg IV daily (A1). ○ If the organism has intermediate susceptibility to fluconazole and the patient is stable, the dose can be increased to 800 mg/day. ○ Doses should be adjusted for renal function. • Not neutropaenic and a fluconazole resistant organism: Caspofungin (B1), Voriconazole (C111), or a lipid preparation of Amphotericin B (C111) may be used according to susceptibility of organism, patient tolerance and comparative cost. The maintenance dose of voriconazole is 3mg/kg IV bd for treatment of candidemi

Answer 8

- Emerging drug resistant yeast responsible for hospital outbreaks - Risks: chronic disease, immunocompromised, presence of indwelling medical devices - Antifungal resistance is common - including echinocandins and amphotericin B - 1st line: echinocandins - Strict infection control, single room isolation, require hydrogen peroxide to kill

Answer 9

- Previous antimicrobial therapy, prolonged hospital stays, requirement for ICU/dialysis, invasive procedures and indwelling urinary or venous catheters - MRSA: maori and pacific ethnicity - ESBL + VRE: rest home facilities - CRO (NDM-1): patients who have received medical care in India or Pakistan

Answer 10

* Resistance conferred by the mecA gene, carried on a mobile genetic element – the Staphylococcal cassette chromosome (SCCmec) * mecA encodes an additional penicillin binding protein – PBP2a * PBP2a is a transpeptidase (cross-links bacterial cell wall peptidoglycan) with poor affinity for ALL the beta-lactam antibiotics (penicllins, cephalosporins (I-IV)*, carbapenems)

Answer 11

* Antibiotic of choice for invasive infections is VANCOMYCIN (glycopeptide) * Alternatives: - Daptomycin (cyclic lipopeptide – cell membrane) has non-inferiority to vanc., but poor CNS penetration and also inactivated by surfactant. - Teicoplanin (also a glycopeptide – cell-wall), has comparable efficacy to vanc. but also requires therapeutic drug monitoring and often under dosed - Ceftaroline (5th gen-cephalosporin) has high affinity for PBP2a. Newer agent without a large evidence base. ○ Poorer Alternatives - Quinupristin- Dalfopristin (streptogramin – 50s ribiosome, but bacteriocidal) – side effects (myalgias, infusion reactions, nausea) often limits use - Linezolid (oxazolidinone – 50s ribosome) has both good oral bioavailability and tissue penetration, but prolonged use limited by risk of bone marrow suppression and peripheral neuropathy. Bacteriostatic. - Clindamycin (lincosamide – 50s ribosome) also has high oral bioavailability, but not recommended for endovascular infections. Bacteriostatic. Sulfamethoxazole-trimethoprim has been shown to be inferior to vancomycin for endovascular infections, best for skin/soft-tissue infections. Bacteriostatic

Answer 12

* VRSA - Acquisition of a plasmid containing the mobile transposon with the vanA gene from vancomycin-resistant Enterococci. * This alters the (unlinked) peptidoglycan terminus from D-Ala D-Ala to D-Ala D-Lac * Depending on the isolate, treatment options include daptomycin with another agent (linezolid, TMP-SMX, gentamycin, or rifampicin) • VISA – vancomycin-intermediate S.aureus (MIC 4-8ug/ml). Mechanism thought to be due to cell-wall thickening. • hVISA – heterogenous VISA – isolates appear to have a susceptible MIC for vancomycin, but have a subpopulation that are VISA. Population analysis profile required to detect these. Treatment: Teicoplanin generally avoided, see previous slide for options.

Answer 13

* Enterococci have intrinsic resistance to multiple antibiotics – celphalosporins, macrolides, glycopeptides, tetracylines, and fluoroquinolones. Enterococcus faecium is typically resistant to amoxicillin, while E faecalis is often sensitive to amoxicillin. * Phenotypically there are five groups of vancomycin resistance (Van A to E), with VanA and VanB typically seen in E faecium and E faecalis. * The vanA gene cluster confers resistance to both vancomycin and teicoplanin, while the vanB gene cluster only confers vancomycin resistance. Treatment options are limited, but include linezolid, daptomycin, tigecycline and quinupristin-dalfopristin.

Answer 14

* The Ambler classification scheme divides beta-lactamases into four major groups, based on amino acid homology. The majority of ESBLs belong to Ambler class A, and include the CTX-M, SHV, and TEM subtypes. * Treatment options are limited to carbapenems, ceftazidime-avibactam, ceftolozane (a 5th gen cephalosporin)-tazobactam and non beta-lactams. * Resistance to aminoglycosides and trimethoprim-sulfamethoxazole often carried on the same plasmid. * Recently the MERINO study demonstrated that piperacillin-tazobactam was inferior to meropenem for treatment of ESBL bacteraemia.

Answer 15

- They are an ESBL subgroup • Enterobacter species, Serriatia spp, Citrobacter freundii (& braakii), Acinetobacter (& Aeromonas) spp, Proteus (not mirabilis), Providencia spp, Morganella morganii • Initially appear to be sensitive to beta-lactam antibiotics, but treatment failures seen due to the presence of an inducible cephalosporinase/beta-lactamase – chromosomal AmpC (Ambler class C) • This confers resistance to most beta-lactams and beta-lactam/beta-lactamase/inhibitors, with the exceptions of the carbapenems, and the fourth generation cephalosporin cefepime. • May not be reported as an “ESBL”, or reported with sensitivity to beta-lactams • Treatment options include carbapenems (ertapenem has poor activity against Acinetobacter), or non-beta-lactams. • Piperacillin-tazobactam has also been used as it is a poor inducer of AmpC Newer non-beta-lactamase inhibitors, like avibactam, have been shown to be effective in combination with ceftazidime

Answer 16

Mechanisms of resistance include - efflux pumps - porin mutations, and - carbapenemase production. • The three main groups of carbapenemases are the: ○ Klebsiella pneumoniae carbapenemase - KPC (Ambler Class A), ○ metallo-beta-lactamases – NDM (New Dehli metallo-beta-lactamase), IMP (imipenem-resistant Pseudomonas), and VIM (Verona integron-encoded metallo-beta-lactamase) (Ambler class B) ○ Oxacillinases – OXA-48, OXA-181 (Ambler Class D) • The metallo-beta-lactamases have a zinc moiety at their active site, while the other classes have serine NOTE: - Ambler class C - presence of an inducible cephalosporinase/beta-lactamase -chromosomal Amp C - In the ESCAPPM organisms - Tx: carbapenems and non beta lactams

Answer 17

- Treatment options are limited * Colistin (polymyxin – bacterial cell membrane) effective for most CROs, but use limited by RENAL and NEUROTOXICITY. Used as last resort for gram NEGATIVE. * Tigecycline (glycylcycline – 30s ribosome), bacteriostatic, poor tissue penetration, often used in combination rather than monotherapy * Amikacin (aminoglycoside – 30s ribosome), has the expected aminoglycoside toxicities, resistance mechanisms to the aminoglycosides often carried on the same plasmid * Fosfomycin (phosphonic acid derivative - bacterial cell wall) efficacy in cystitis, but data otherwise lacking * Dual carbapenem therapy has been shown to have some efficacy in case reports for KPC infections * Amikacin (aminoglycoside – 30s ribosome), has the expected aminoglycoside toxicities, resistance mechanisms to the aminoglycosides often carried on the same plasmid * Ceftazidime-avibactam, ceftaroline-avibactam has efficacy against the OXA and KPC groups but not NDM

Answer 18

- Last resort for gram negative bacteria | - Binding to LPS and phospholipids in the outer membrane

Answer 19

DNA damage

Answer 20

Cause loss of selective cell membrane permeability

Answer 21

``` Inhibit replication and transcription Inhibit gyrase (unwinding enzyme) ```

Answer 22

Inhibit RNA polymerase

Answer 23

- Rifampicin: inhibit RNA polymerase (bactericidal) SE: red/orange urine, ramp up cytochrome P450 (increases metabolism of multiple medications) including oral anticoagulants, oral contraceptives, glucocorticoids, digitoxin, quinidine, methadone, hypoglycemics, and barbiturates. - Isoniazid: MOA: Prodrug and needs to be converted into its active metabolite by bacterial catalase peroxidase (encoded by KatG). Prevents cell wall synthesis by inhibiting the synthesis of mycolic acid SE: INH - affect neurons (peripheral neuropathy) and hepatocytes - Pyrazinamide: intracellular acidification SE: hepatitis, skin, polyarthralgia, gout - Ethambutol: cell wall arabinogalactan SE: optic neuropathy inhibits arabinosyltransferase → ↓ carbohydrate polymerization → prevention of myobacterial cell wall synthesis (bacteriostatic effect)

Answer 24

Affects NUCLEAR DIVISION Inhibits fungal mitosis by binding to intracellular microtubular protein Use: jock itch, athlete's foot, and ringworm; and fungal infections of the scalp, fingernails, and toenails.

Answer 25

Nucleic acid synthesis Fluorine analogue of cytosine Deamination to 5-fluorouracil, which is incorporated into fungal RNA inhibiting protein synthesis, inhibits thymidylate synthase after conversion of flucytosine to 5-fluorodeoxyuridine and fluorodeoxyuridine monophosphate – inhibitor of thymidylate synthetase (DNA synthesis) – active against cryptococcus, candida; used as combination therapy for cryptococcus – oral or IV formulations – dose-adjustment if renal impairment

Answer 26

Coxiella burnetii is the causative agent of Q fever. Q fever is a zoonotic disease seen mostly in people who work with farm animals - slaughterhouse workers, farmers, shepherds Diagnosis - PCR early (or tissue) - Then phase 2 - Then phase 1 Pathophysiology - Phase I antigens: when C brunetii is highly infectious - Phase II: when C burnetii is less infectious - Antigenic shift essential to differentiate between acute and chronic - C burneti escapes macrophage phagocytosis by producing superoxide dismutase to inactivate phagolysosome enzymes and inhibiting cathepsin fusion Acute Q Fever: few C burnetii organisms and stronger cell response to pathogen Chronic Q Fever: multiple C burnetii organisms and weaker cell response - survive in macrophages and monocytes - Present as cholestatic hepatitis or, occasionally, atypical pneumonia; however, symptoms can be nonspecific so Q fever should be considered in any undiagnosed febrile illness. - Q fever endocarditis, bone and joint infection, and infection of aneurysms and vascular grafts are rare and can be difficult to diagnose. - Acute Q fever usually resolves spontaneously within 2 to 6 weeks. There is no value in treating nonpregnant patients after spontaneous recovery; however, patients with cardiac valve disease or vascular grafts require careful investigation and follow-up to exclude the development of endocarditis or graft infection. Diagnosis - Acute Q Fever: 4 fold or greater increase in C. burnetii antibody titre to phase II antigen by indirect immunofluorescent (Anti pHase II ab IgG titre > 200, IgM >50, IgM ab against phase II antigens > antibodies against phase I antigens - Chronic Q Fever: antiphase I antibody IgG titres > 800 or persistently high levels of anti phase I ab 6 months after completing therapy - Antibodies against phase I antigens > antibodies against phase II antigens Acute Infection: - Doxycycline 100mg BD for 14 days 2nd line: azithromycin - If pregnant: bactrim + folic acid Chronic: - Doxycycline + hydroxychloroquine for > 18 months - 2nd line: rifampin + doxycycline/ciprofloxacin

Answer 27

Oral valganciclovir | IV ganciclovir

Answer 28

``` HSV1 - encephalitis HSV2 - meningitis HHV3 - varicella HHV4 - EBV Hepatitis, neutropenia HHV5 - CMV Atypical lymphocytosis, hepatitis HHV6, 7 - roseola HHV8 - kaposi's sarcoma ```

Answer 29

C. Commence anidulafungin and remove line If you see a line in the exam - pull it out except S epi Kruzei - fluesi so fluonazole does not work

Answer 30

- Prophylactic: Amoxicillin 250mg daily or phenoxymethylpenicillin 250mg BD for 3 years post splenectomy for other health or lifelong if immunocompromised or prior OPSI Vaccinations - Pneumococcus: PCV13 then PPV23 8 weeks later and then PPV23 5 yearly (x3) Give PCV13 before PPV23 - conjugate prior to polysaccharide to prevent hypersensitivity. - Meningococcus: Quad meningococcal conjugate vaccine - 4MenCV ACWY 2 doses 2 months apart and then 5 yearly Meningococcal B vaccine (recombinant B) - MENBV 2 doses 2 months apart - Haemophilus influenza - Influenza annually \ Streptococcus pneumoniae is the commonest cause of sepsis after splenectomy and the immunisation and prophylaxis are incompletely effective.

Answer 31

Voriconazole can cause a photosensitive dermatitis and patients should be advised to slip, slop, slap!!

Answer 32

- Natural reservoir: fruit bat - Fever, weakness, diarrhoea - Incubation period typically 11 days - Cell surface adhesion (eg: endothelium) mediated via glycoprotein 1 and 2 - Diagnosis: PCR positive 1 day prior to symptoms)

Answer 33

Transmission: mosquito borne transmission (Aedes aegypti), mother-infant, sexual Clinical: - Acute febrile illness (rash, fever, arthralgia, conjunctivitis, myalgia, headache) • Most common symptoms are rash lasting a median of 5.5 days (97%), pruritus (79%), headache (66%), arthralgia (63%), myalgia (61%) and non-purulent conjunctivitis (56%) • Fever is present in approximately 50% of cases and lasts for less than 1 day - Neurological including guillian barre syndrome - Adverse fetal outcomes: microcephaly Diagnosis: PCR, IgM Mx: symptom management Prevention: mosquito avoidance, reduce sexual exposure

Answer 34

Presentation - Acutely swollen and painful lower limb or abdominal wall - Severe pain >>>clinical signs - High fevers RF - Diabetes - IVDU - Alcoholism - Local trauma - Surgery or bowel pathology POLYMICROBIAL: mixed anaerobes, streptococci, staphylcocci, enterobacerace Mx: - Surgical debridement - IV meropenem OR IV tazocin + IV vancomycin + either clindamycin/lincomycin

Answer 35

Streptococcal toxic shock syndrome requires isolation of S. pyogenes from a hypotensive patient with two of the following signs: kidney impairment, coagulopathy, hyperbilirubinaemia, adult respiratory distress syndrome, generalised rash or soft tissue necrosis. Primary infection: wound skin Mx: IV benpen plus either IV clindamycin or lincomycin intravenous immunoglobulin (IVIg) (adult and child) 2 g/kg intravenously, as a single dose as soon as possible but not later than 72 hours. It is reasonable to give the dose in divided doses if it is not possible to give a single dose.

Answer 36

– toxin-producing strain, S. aureus – association with tampon use, but source may also be other sites (wounds, respiratory tract). – clinical: fever, V&D, shock develops within 24 hours, diffuse maculo-erythematous rash, non-purulent conjunctivitis – B.C. usually negative – management: flucloxacillin +/- clindamycin

Answer 37

Hydrocortisone group: shock reversed more quickly, but more episodes of superinfection (including new sepsis and septic shock).

Answer 38

- Nocardia asteroides, Nocardia farcinicia, Nocardia brasilinesis - Gram positive, branching bacteria - Environmental, soil, organic matter, water Nocardiosis is caused by environmental Gram-positive Actinobacteria of the Nocardia genus. It is found throughout Australia but more commonly in tropical and subtropical regions. Clinical: - Cutaneous/lymphocutaneous - Pulmonary - Systemic + CNS - Single or multiple skin lesions can occur in immunocompetent individuals. - Disseminated disease usually occurs in immunocompromised patients, and is commonly associated with central nervous system infection with brain abscesses. - Pulmonary Nocardia ranges from mild acute or mild chronic disease with minimal or no changes on chest X-ray, to severe multilobar disease with high mortality. - Consider testing patients with severe or disseminated Nocardia for an immune system disorder (eg HIV). - Except in immunocompetent patients with localised cutaneous disease (in whom imaging should be considered on a case-by-case basis), chest X-ray and brain computed tomography (CT) or magnetic resonance imaging (MRI) (both with contrast) are recommended to assess for pulmonary and neurological disease. Diagnosis - Culture: look for branching Gram-positive bacilli on microscopy and culture of skin swabs, pus and sputum.

Answer 39

Nocardiosis cases can be divided into three categories based on patient factors, severity, and site of disease: (1) Mild disease: nonsevere disease in immunocompetent patients with localised cutaneous disease. BACTRIM (2) Moderate disease: nonsevere disease in: - immunocompetent patients with more extensive cutaneous disease - immunocompromised patients with cutaneous disease (including those with immune compromise caused by a chronic medical condition such as diabetes, chronic kidney disease or hazardous alcohol use) - any patient with mild or moderate pulmonary disease. BACTRIM + CEFTRIAXONE/LINEZOLID (3) Severe disease: including CNS disease with brain abscess, disseminated disease and severe pneumonia. BACTRIM + LINEZOLID + EITHER AMIKACIN/IMIPENEM/MEROPENEM

Answer 40

- Toxoplasmosis gondii - parasite - Risks increased with defects in T cell mediated immunity, eg: haematological malignancy, BMT, SOT, HIV Life Cycle - Cats shed oocyst - Sporulation occurs outside cat 1-5 days later (required to be infectious) - Tachyzoite (human intestine) - Cyst (tissue) ``` Clinical - CNS - Myocardial - Pulmonary - Chorioretinitis - ocular pain, reduced acuity - Diagnosis - Serology - Isolation from tissue especially tachyzoites - PCR - high specificity for CSF - CT: enhancing lesions ``` Mx Pyrimethamine + Calcium folinate + either sulfadiazine/clindamycin OR bactrim -

Answer 41

- Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of molds called mucormycetes. - Rare - Absidia spp, Mucor, Rhizopus (morphologic differences) - Risk factors: acute leukaemia, solid organ transplantation, diabetic ketoacidosis, iron overload, desferrioxamine therapy, burns - Angio-invasive, tissue necrosis++ - Involvement of paranasal sinuses, with dissemination to brain & orbit ``` Treatment: – underlying condition e.g. DKA – debridement* – antifungal therapy: amphotericin (lipid formulations) – adjuvant: granulocyte infusions? ```

Answer 42

- Budding yeast - Ubiquitous, isolated in river red gum, forest red gum, pigeon excreta - C. neoformans var gattii (immunocompetent hosts), var neoformans (immunodeficient hosts) Clinical: – CNS – var gattii lower mortality but prolonged course – pulmonary –may be asymptomatic – other –skin, sinusitis, viscera Diagnosis: – CSF –increased opening pressure, decreased glucose, increased protein, increased lymphocyte count – culture –CSF, BC (HIV), respiratory specimens – histology – Indian ink – antigen detection –latex agglutination Management: – amphotericin B & flucytosine, 6/52; fluconazole – HIV – shorter course of initial therapy, maintenance fluconazole – hydrocephalus

Answer 43

Until 24 hours post abx

Answer 44

Prevention of CVC-related bloodstream infection: – educating & training HCW – maximal sterile barrier precautions for insertion – 2% chlorhexidine preparation for skin antisepsis – avoid ‘routine’ replacement of CVC – antiseptic/antibiotic impregnated short-term central venous catheters if rate of infection is high despite adherence to above strategies – ‘bundle’ strategy • Antibiotic ‘locks’ – 3 studies in neutropenic patients, LT CVC – heparin + vancomycin or (vancomycin+ciprofloxacin) – reduced rate of CR-BSI and longer time until CR-BSI – Concern re: VRE; not routinely recommended

Answer 45

* Toxin A = enterotoxin (specific CHO intestinal receptors); * Toxin B = cytotoxin; disrupts intercellular tight junctions ``` • Clinical: – antibiotic-associated diarrhoea – colitis – toxic megacolon – perforation – (asymptomatic) ``` • Diagnosis: culture, toxin A/B assay (EIA)

Answer 46

1st episode of mild/moderate: - PO Metronidazole or PO vancomycin 1st recurrence or refractory - PO vancomycin or fidaxomicin (inhibition of RNA polymerase) 2nd and subsequent recurrences - Faecal transplant - Vancomycin or fidaxomicin Severe - leucocytosis, severe abdo pain, elevated creatinine, elevated lactate, low albumin, high fever, organ dysfunction - PO Vancomycin + IV metronidazole - Surgical intervention – faecalmicrobiota transplantation (refractory/recurrent infection) – bezlotoxumab (monoclonal antibody; prevention of recurrence)

Answer 47

Used for gram negative mcr-1 – gene conferring plasmid-mediated resistance to colistin – Asia, Europe, Africa, N. America, S. America (Enterobacteriaceae) • Colistin: mode of action/resistance – binds to lipopolysaccharides/phospholipids in cell membrane of GNB --> leakage of intracellular contents & bacterial death. – binds/neutralizes LPS & prevents effects of endotoxin – mcr-1 a member of phosphoethanolaminetransferase enzyme family --> results in addition of phosphoethanolamine to lipid A. • Spread from veterinary to human domain? – mcr-1-positive bacteria more frequently observed in animals – colistin use in pig production – ‘One Health’ approach to surveillance/future research

Answer 48

- A disease caused by infection with freshwater parasitic worms in certain tropical and subtropical countries. - Middle east, africa, latin america S. mansoni*, S. haematobium*, S. japonicum, S.mekongi, S. intercalatum * Infection: snail=intermediate host, penetration of intact skin by cercarial lavae in fresh water * Urinary tract: S. haematobium; Bowel: S. masonii, S. japonicum, S. intercalatum • Clinical: - pruritic rash within days - systemic febrile illness (Katayama fever) 4-8 weeks later - fibrotic response in urinary tract or gut months-years later, chronic infection (colitis, portal HT, urolithiasis, SCC bladder) • Diagnosis: - Identification of eggs in stool, urine or biopsy samples - serology, eosinophilia • Management: praziquantel 2 doses, 4 hours apart Acute schistosomiasis syndrome (Katayama fever) occurs 3 to 8 weeks after infection and is a systemic hypersensitivity reaction to schistosome antigens and circulating immune complexes. Treatment includes prednis(ol)one followed by praziquantel.

Answer 49

Infection: laval penetration of intact skin in contact with moist faecally contaminated soil Clinical: diarrhoea, abdominal pain, urticarial rash Tx: ivermectin or albendazole

Answer 50

• Leptospirosis is caused by the spirochaete Leptospira interrogans (serogroup L. icterohaemorrhagiae), classically being spread by contact with infected rat urine. • Epidemiology ○ leptospirosis is commonly seen in questions referring to sewage workers, farmers, vets or people who work in an abattoir ○ however, on an international level, leptospirosis is far more common in the tropics so should be considered in the returning traveller • Weil's disease should always be considered in high-risk patients with hepatorenal failure • Features ○ the early phase is due to bacteraemia and lasts around a week ▪ may be mild or subclinical ▪ fever ▪ flu-like symptoms ▪ subconjunctival suffusion (redness)/haemorrhage ○ second immune phase may lead to more severe disease (Weil's disease) ▪ acute kidney injury (seen in 50% of patients) ▪ hepatitis: jaundice, hepatomegaly ▪ aseptic meningitis • Investigation ○ serology: antibodies to Leptospira develop after about 7 days ○ PCR ○ culture ▪ growth may take several weeks so limits usefulness in diagnosis ▪ blood and CSF samples are generally positive for the first 10 days ▪ urine cultures become positive during the second week of illness • Management ○ high-dose benzylpenicillin or doxycycline

Answer 51

Burkholderia pseudomallei (gram negative rod, soil saprophyte) • Distribution: S.E. Asia, Northern Australia • Outbreaks, cases associated with rainfall • Risk factors for infection: diabetes, alcoholism, CJD, CF • Clinical: pneumonia, abscesses (spleen, prostate), osteomyelitis, septic arthritis, skin & soft-tissue infection, high mortality in sepsis Pneumonia is the most common presentation but can cause abscesses in any organ (especially spleen and prostate). • Relapses common, LT eradication therapy required • Diagnosis: - culture of B pseudomallei - definitie diagnosis - serology - PCR and antigen detection • Management: - Non-neurological: ceftazidime or meropenem - Neurological: meropenem For patients with neurological infection, osteomyelitis, septic arthritis, genitourinary infection (including prostatic abscess), or skin and soft tissue infection, add to the initial therapy regimens above: Bactrim + folic acid Consider GCSF for critically ill patients

Answer 52

Chromosome 8 translocation - deregulation of C-MYC oncogene

Answer 53

``` CAG A gene Vacuolating cytotoxin (VacA) ```

Answer 54

D. EBV-associated Burkitt’s lymphoma has been associated with chromosome 12 translocation and de-regulation of the c-MYC oncogene

Answer 55

A - Penicillinases (TEM, SHV, CTX-M) B - Metalloenzymes (NDM, VIM, IMP) C - Cephalosporinases (AmpC) D - Oxacillinases (OXA)

Answer 56

``` Amp-C type ESCAPPM organisms - Enterobacter - Serratia - Citrobacter - Actinetobacter - Providencia - Proteus - Morganella ```

Answer 57

Mainly - Klebsiella - E coli - Salmonella - Proteus - Enterobacter - Citrobacter - Serratia - Pseudomonas

Answer 58

Carbapenem Colistin Amikacin (fosfomycin for UTI)

Answer 59

- Zinc dependent - Especially in pseudomonas and actinobacter - Plasmid mediated usually - Hydrolyse all beta lactams - Hydrolyse carbapenems - Susceptible to ion chelators like EDTA - New delhi version Tx; Ceftazidime-avibactam combined with aztreonam

Answer 60

- Travel - Hospital contact - Found in bacteria in puddles and tap water - Swedish backpackers Tx: limited but may include colistin, cefiderocol, tigecycline

Answer 61

- Associated with community acquired liver abscess - Also bacteraemia and endophthalmitis - Hypermucoviscous capsule Tx: ceftriaxone

Answer 62

- MOA: inhibit protein synthesis Good activity against gram positives plus mycobacteria and nocardia - Good tissue penetration and bioavailability SE - GI upset - Cytopenia - Neuropathy - MAO inhibition Avoid SSRIs, tramadol, pethidine

Answer 63

- Cyclic lipopeptide - MOA: binds to cell membrane and leads to inhibition of synthesis of DNA, RNA, protein --> bactericidal - Bactericidal activity against most gram positives

Answer 64

- Derivative of minocycline - Protein synthesis inhibitor Essentially bacteriostatic - Active against many gram NEGATIVES - SE: GI upset

Answer 65

MOA: - Binds to lipopolysaccharides and phospholipids in outer cell membrane - Leads to disruption of outer cell membrane, leakage and cell death - Gram negative bacteria SE: - Renal toxicity - Neurotoxicity

Answer 66

MOA - Inhibits MurA enzyme - Inhibits bacterial cell wall biogenesis - Bactericidal Mainly for resistant UTI SE: GI upset

Answer 67

- Broad spectrum - Good tissue penetration and bioavailability - Associated with C diff SE - QT Interval - Tendons - Eyes - C diff

Answer 68

- Broad spectrum - Good tissue penetration and bioavailability - Associated with C diff SE - QT Interval - Tendons - Eyes - C diff

Answer 69

Triad of - Tenosynovitis - Dermatitis - Polyarthralgia without purulent arthritis Cef + azithro

Answer 70

- L1/2/3 serovas of Chlamydia trachomatis - Primary: genital ulcers - Secondary: swollen nodes +/- anorectal syndrome - Heterosexual men and women - Late: fibrosis and strictures - PCR sequencing Doxycycline 100mg BD for 3 weeks - If pregnant - azithromycin

Answer 71

Whipple's disease is a rare multi-system disorder caused by Tropheryma whippelii infection. It is more common in those who are HLA-B27 positive and in middle-aged men. Clinical Features • Migratory large joint arthralgias • Malabsorption: diarrhoea, weight loss, abdominal pain • lymphadenopathy • skin: hyperpigmentation and photosensitivity • pleurisy, pericarditis • neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus Investigations • Small bowel biopsy or PCR jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules Tx: Ceftriaxone then long-term Bactrim

Answer 72

- Anthrax is a rare infectious disease caused by Bacillus anthracis, a gram-positive spore-forming bacterium that is found in soil. - Human infection usually results from contact with infected livestock or infected animal products (e.g., wool or meat). - Depending on the route of entry, three distinct clinical syndromes can occur: inhalation anthrax, cutaneous anthrax, and gastrointestinal anthrax. ``` CUTANEOUS Cutaneous anthrax (the most common form) presents initially as a papular lesion, which later becomes vesicular, and eventually forms a necrotic eschar. ``` INHALATION Inhalation anthrax results in hemorrhagic mediastinitis and presents with fever, acute, nonproductive cough, retrosternal chest pain, and/or pleural effusion. GASTROINTESTINAL Gastrointestinal anthrax, which is very rare, causes gastrointestinal ulceration, which results in hematemesis and/or bloody diarrhea. DIAGNOSIS + MANAGEMENT The diagnosis of anthrax is confirmed by the microscopic evidence of B. anthracis. Mortality is high but swift treatment with antibiotics (e.g., fluoroquinolones, linezolid, meropenem) can increase survival. Prognosis of cutaneous anthrax is usually better than that of inhalation and gastrointestinal anthrax .

Answer 73

• Toxins A, B, & E bind to pre-synaptic nerves • Prevent release of Acetyl Choline • 1 gram could kill 1.5 million! • Cranial nerves then symmetrical descent • No sympathetic or sensory involvement • Diagnosis by clinical suspicion, check food, EMG • Supportive treatment, +/- antitoxin, penicillin

Answer 74

Rifampicin – induction of cytP450 • Warfarin, voriconazole, protease inhibitors, anti-epileptic agents, methadone, tamoxifen, SSRIs, CyA, Tacro, Corticosteroids Rifampin has been reported to increase the warfarin requirements in human subjects ingesting these agents simultaneously. The concomitant administration of rifampin and warfarin resulted in the need for an unusually high maintenance dose of warfarin (20 mg per day) in order to produce a therapeutic effect.

Answer 75

Reduced absorption with Ca, Fe, Zn, antacids

Answer 76

Voriconazole, macrolides, moxifloxacin, pentamidine, | mefloquine, halofantrine

Answer 77

Doxycycline Ciprofloxacin Voriconazole

Answer 78

Linezolid, metronidazole, isoniazid, DDI, DDC

Answer 79

Predominantly vestibular rather than cochlear Vertigo and hearing loss are relatively rare Associated with cumulative dose - can be detected by bedside head impulse test

Answer 80

- Anaemia - Thrombocytopenia - Neuropathy - Lactic acidosis - Serotonin syndrome

Answer 81

- Increasing age: advanced age x10 folder higher than in younger patients - Recent hospitalisations - use of PPI Gastric acid suppression: 1.4-2.75x higher ``` Antibiotics Frequently Associated - Clindamycin - Fluoroquinolones - Penicillin - Cephalosporin (2nd/3rd/4th) - Carbapenem ``` Occasionally Associated - Macrolides - Penicillins - Cephalosporins (1st gen) - Bactrim - Sulfonamides Rarely Associated - Aminoglycosides - Tetracyclines - Tigecycline - Chloramphenicol - Metronidazole - Vancomycin

Answer 82

- Visual symptoms (blue/green aura) - Photosensitivity - Purplish skin discolouration - Cholestatic LFT - CYP interactions

Answer 83

- Tendinopathy - QT prolongation - C diff

Answer 84

Elevated CK

Answer 85

Peripheral neuropathy | Pulmonary fibrosis

Answer 86

Peripheral neuropathy Ataxia Dysarthria

Answer 87

Hearing loss | Increased cardiac and all cause mortality

Answer 88

- Metronidazole - Cotrimoxazole - Clindamycin - Ciprofloxacin and other quinolones - Doxycycline - Rifampicin - Linezolid - Fluconazole - Amoxycillin - only beta lactam with highish bioavailability

Answer 89

B. Gentamicin Causes lung infection Macrolides and fluoroquinolones should be the drugs of choice for the treatment of established Legionellosis.

Answer 90

SEECSY - bloody diarrhoea doesn't sound SEXY ``` Salmonella E Coli (EHEC, ETEC) Entamoeba (Protozoa) Campylobacter Shigella Yersinia ```

Answer 91

Vibrio | Norovirus

Answer 92

Staph aureus enterotoxin Bacilus cereus Both incubation period 1-6 hours

Answer 93

SSCY - Shigella - Salmonella - Campylobacter - Yersinia

Answer 94

E coli O157:H7

Answer 95

Upper Small Bowel = Secretory Diarrhoea = Watery Diarrhoea - Vibrio cholera - Enterotoxigenic E coli (ETEC) - Enteropathogenic E Coli (EPEC) - Rotavirus - Norovirus - Giardia - Cryptosporidium - Bacillus, Clostridium, Staph aureus, vibrio cholearea Distal Small Bowel + Colon = inflammatory colitis - Shigella - Salmonella - Campylobacter - Yersinia - C diff

Answer 96

An interstitial pneumonitis with foamy intra-alveolar exudate Pneumocystis pneumonia (PCP) or pneumocystosis is a form of pneumonia, caused by the yeast-like fungal organism Pneumocystis jirovecii. The organism is confined to the alveolar space of the lung and produces debris and cysts in the alveolar space with interstitial infiltration of lymphocytes and plasma cells. As a result, it can cause profound disturbance of oxygen exchange and fatal hypoxaemia if left untreated.

Answer 97

- Legionella pneumophila is a Gram negative bacillus that is ubiquitous in the environment. - The infection causes a flu-like illness with a dry cough, headache, confusion and delirium. - Gastrointestinal upset is common, with diarrhoea and ileus. - Focal neurological signs can develop. - Bloods often show a normal white cell count with lymphopenia (with or without thrombocytopenia, or pancytopenia). - Sodium is often low, due to a syndrome of inappropriate antidiuretic hormone. - 50% of patients have abnormal renal and liver function, and acute kidney injury can develop. Creatinine kinase can be raised. - Legionellae do not grow on standard culture media, but require specific supplemented media; they grow best at a low pH. - Diagnosis is most commonly with antigen testing in the urine, but direct fluorescent antibody staining or serology can be used. TX Erythromycin or clarithromycin are the antibiotics of choice; alternatives include doxycycline, cotrimoxazole or ciprofloxacin.

Answer 98

Patients with C3 deficiency, be it absolute, relative, genetically determined (autosomal dominant or recessive), or due to properdin deficiency, are predisposed to recurrent infection with encapsulated proteins, particularly N. meningitidis. C3 is the point at which the classical, alternative, and lectin complement pathways converge.

Answer 99

C1qrs, C2, and C4 are strongly associated with systemic lupus erythematosus (SLE).

Answer 100

C5 deficiency is associated with Leiner's disease, a syndrome of recurrent diarrhoea, wasting, and generalised seborrhoeic dermatitis presenting in infants.

Answer 101

• Ubiquitous moulds and opportunists • A fumigatus, A flacus, A niger predominate • Environmental source • Typically alveolar infection, pulmonary angio-invasion and then dissemination • Elusive but important diagnosis • EORT/MSG Diagnostic Criteria for IFD (invasive fungal diseases) ○ Proven: culture/histology for sterile site ○ Probable: host, clinical or mycological factors ○ Possible: host, clinical or mycological factors • Diagnosis ○ Radiology: chest, sinuses, brain § Air-crescent sign ○ Identification of organism from tissue or respiratory samples by histology (hyphae), microscopy or culture ○ Non culture diagnostics § Galactomannan antigen - serum or bronchoalveolar lavage § PCR, eg: whole blood or tissue • Treatment: ○ Surgery: sinus surgery, lobectomy or decortication ○ Optimise host response, eg: GCSF, decrease steroid, granulocyte infusions ○ Specific antifungal therapy § Voriconazole or isavuconazole or liquid amphotericin § 6-12 weeks depending on radiologic response ○ Combination AFT uncertain benefit ○ Secondary prophylaxis • Prevention ○ Optimise environment, eg: HEPA filtration, control of building works ○ Mould active antifungal prophylaxis: Posaconazole, itraconazole or micafungin ○ Amphotericin IV/Neb off label

Answer 102

B. Verapamil

Answer 103

B. ICD - it treats risks but doesn't treat the VT