Infectious diseases Flashcards

Question

What are the treatment options for organisms that produce ESBLs?

Answer 1

1. Carbapenems 2. Ceftazidime - avibactam 3. Ceftolozane - tazobactam 4. Aminoglycosides e.g. gentamicin, amikacin 5. Bactrim 6. Fluoroquinolones

Answer 2

1. Nitrofurantoin is 1st line if susceptible & renal funcion ok - eGFR >40 2. PO fosfomycin 3. PO pivmecillinam 4. Bactrim or fluoroquinolones

Answer 3

Enterobacter Serratia Citrobacter Acinetobacter, aeromonas Proteus (but not Proteus mirabilis) Pseudomonas Providencia Morganella

Answer 4

AmpC is an Ambler Class C chromosomally encoded, inducible beta lactamase Induced by cell wall breakdown products When expressed in large amounts, ampC conveys resistance to 1st - 3rd gen cephalosporins, augmentin DF, tazocin, penicillins Susceptible to carbapenems, aminoglycosides (gentamicin), cefepime, bactrim, ciprofloxacin

Answer 5

Exposure to antibiotics - > cell wall breakdown products Ampicillin & cephazolin are strong inducers of ampC -> therefore ESCAPPM organisms should always be considered resistant Organisms with highly inducible ampC -> Klebsiella aerogenes, Enterobacter, Citrobacter -20% chance of treatment failure with 'susceptible' antibiotics Providencia & morganella are less likely to have ampC induced

Answer 6

Carbapenems 1st line Cefepime Ceftazidime-avibactam Tazocin - weak inducer of ampC

Answer 7

Colistin resistance identified in 2015 Found in livestock & waterways Plasmid mediated Encoded by MCR-1 = mobilised colistin resistance 1

Answer 8

- very potent, novel, second generation beta lactamase inhibitor - binds to beta-lactamase enzyme via reversible cyclisation (rather than suicide inhibitio) - it is released / regenerated to continue to inhibit other molecules - can inhibit class A (e.g. KPC, ESBL), class C (ampC), class D (OXA-48), BUT no activity against metallo-beta-lactamases **for KPC ceftazidime-avibactam is the best

Answer 9

- usually combination therapy - monotherapy associated with high mortality 40% - combination therapy includes colistin backbone PLUS other agent - colistin = polymyxin E - tigecycline - inhibits ribosome 30s subunit, bacteriostatic, poor tissue penetration - amikacin - aminoglycoside - inhibits 30s - fosfomycin - oral, efficacy in cystitis but otherwise data is lacking - dual carbapenem therapy may be effective for KPC - Ceftazidime - avibactam for class A, class C & class D carbapenemases (but NOT against class B)

Answer 10

1. Class A - Klebsiella pneumonia carbapenemase 2. Class B: New delhi metallo-beta-lactamase Imipenem resistant Pseudomonas Verona integron encoded metallo-beta-lactamase 3. Class D Oxacillinases - OXA-48 or OXA-181

Answer 11

Neurotoxicity & nephrotoxicity (nephrotoxicity is more common) Neurotoxicity includes opthalmoplegia, paraesthesias, dysphagia, vertigo, respiratory apnoea

Answer 12

Act against the outer cell membrane of gram negative bacteria - specifically targets phospholipids & lipopolysaccharides. Bind to negatively charged lipopolysaccharides disrupting cell membrane integrity Leading to cell death

Answer 13

Ertapenem has no activity against Pseudomonas Carbapenems generally not effective against VRE, MRSA, E.faecium, chlamydia, mycoplasma, strenotrophomonas maltophilia

Answer 14

1. Env gene encodes surface proteins - gp120 for surface attachment, gp41 for membrane fusion 2. Pol gene encode enzymes - reverse transcriptase, integrase, protease 3. Gag gene encodes structural proteins - capsid, matrix, core & nucleocapsid

Answer 15

-Early infection - gp120-gp41 on HIV binds to CCR5 on CD4+ T cells (Europeans with CCR5 mutation - CCR5 delta 32 homozygote - are immune to HIV infection can bind bc do not present CCR5 on cell surface) -Late infection - mutant HIV can later bind to CD4+ CXCR4 (an aggressive HIV strain can bind both CCR5 & CXCR4) M-tropic HIV - early in infection => SELECTIVELY infects dendritic cells Expresses RANTEs ligand (chemokine 5 ligand) which binds to CCR5 Low ability to induce fusion Moderate pathogenicity T-tropic HIV - later in infection, expresses SDF-1 ligand (AKA chemokine 12 ligand), high ability to induce fusion, high pathogenicity

Answer 16

-M-tropic HIV selectively infects dendritic cells (via RANTES ligand & CCR5; and gp120/gp41 -> CCR5) -dendritic cells travel to lymph nodes & infect CD4+ T cells (INTEGRATION can only occur in resting & terminally differentiated cells) -reverse transcription - NO check points - many mutants formed. - only 0.1% of infected T cells are active and produce HIV - 99% infected cells act as a reservoir for HIV - when CD4 T cells are activated -> produce NFkappaB -> binds to U3 region of 5'LTR region of HIV DNA => causes upregulation of HIV transcription - Release of immature virions containing GagPol polyprotein -> GagPol polyprotein cleaves & activates proteins - Resting memory CD4 T cells harbour latent virus

Answer 17

= primary infection / seroconversion illness -occurs** 3-4 weeks **post transmission -caused by **CD8+ cytotoxic T cells ** **because CD4+ T cells are being killed in large numbers by cytotoxic T cells** - via binding to MHC1 containing HIV peptisdes Specifically also massive loss of CD4 T cells in the GALT - gut epithelial cell apoptosis & break down of tight junctions Associated with high viral load -> eventual CD4 exhaustion leading to decline in HIV replication rate **People with HLA-5701 have better immune response to HIV & slower progression to AIDS because this HLA binds strongly to an important core peptide involved in HIV replication ** Called seroconversion illness because people become Ab positive at this time-point -Lasts 1-4 weeks -Variable severity - may not recall having any illness or hospitalisation ; often assumed to be the or grandular fever Presents with fever, **lymphadenopathy**, respiratory Sx, rash, headache, retro-orbital pain Skin features - seborrheic dermatitis, oral hairy leukoplakia, kaposi sarcoma (deep brown-red papules & plaques), disseminated candiasis, psoriasis, Herpes Zoster, large perianal HSV ulceratyion

Answer 18

At 3-4 weeks post infection At the time of the primary seroconversion illness

Answer 19

>5% eosinophils in CSF is uncommon & suggestive of - parasitic infection - fungal infection - although primarily mononuclear cells with 6-20% eosinophils - neoplastic process - inflammatory process eosinophilic meningitis usually presents with prolonged Sx suggestive of chronic meningitis Have evidence of cerebral involvement as well Fungal causes of eosinophilic meningitis - Candida, coccidioides immitis 3 most important parasitic infections that cause eosinophilic meningitis 1. Angiostrongylus cantonesis (rat lung worm disease) - most common parasitic cause, SE Asia - Malaysia & Thailand, acquired by eating raw or undercooked snails or slugs or crab & shrimp which have eaten them Supportive Rx Anti-helmintic Rx no evidence Usuallyself-limiting & recover completely 2. Gnathostomiasis - endemic in SE Asia, parts of China & Japan, migratory cutaneous swellings is a common presenting feature 3. Baylisascariasis - found in raccoons

Answer 20

Usually after adequate antimicrobial treatment for 3 infections, including index infection and 2 recurrences -> who then present with their 3rd recurrence or 4th infection However, some favour FMT at the 2nd recurrence

Answer 21

- high error rate in reverse transcription producing sequence variation - loss of effector CD4 T cells to fight infection - Latency in resting CD4 T cells - Infection of privileged sites

Answer 22

1. PJP pneumonia 2. CMV retinitis 3. Toxoplasma encephalitis 4. Kaposi sarcoma - HHV-8 - brown lesions on skin & mucosal surfaces 5. Candidiasis - throat, oesophagus, bronchus or lungs (but not mouth) 6. Cachexia & wasting 7. Illnesses associated with herpes virus re-activation - CMV retinitis, EBV-associated hairy leukoplakia on tongue, EBV associated CNS lymphoma 8. HIV-associated dementia 9. Disseminated mycobacterium avium complex / TB 10. Chronic cryptosporidiosis / microsporidiosis

Answer 23

CKD in HIV may be due to HAART or HIV infection Most commonly focal sclerosing GN - presents with nephrotic range proteinuria and renal impairment

Answer 24

DILS = diffuse infiltrative lymphocytosis syndrome -rare, seen in HIV infected patientsm, usually in untreated infection, but can also manifest independent of CD4 T cell count -due to CD8 T cell lymphocytosis and CD8 T cell infiltration into multiple organs -clinical presentation - Sjogren-like disease with sicca signs (dry eyes, dry mouth), bilateral parotiditis, lymphadenopathy, extraglandular involvement -Rx is ART, sometimes steroids

Answer 25

- ELISA testing - very sensitive. Detects the presence of HIV Abs in patient's serum. - Western blot - very specific. No longer done.

Answer 26

- Increase in CD4 count of 50-150 in 1st year - then slower increase of 50-100 per year until steady state is reached - most patients will plateau after 4 yrs. Factors associated with reduced CD4 recovery - Older age, male sex, lower pre-ART CD4 count, certain co-infections e.g. HCV, longer time from initiation of ART to viral suppression ART leads to a near-normal lifespan, especially when ART started early with a high baseline CD4 count Viral load should fall quickly to undetectable levels Rising viral load suggests non-adherence, resistance or both

Answer 27

1. Low baseline CD4 count - usually only if baseline CD4 count <100 (exception is TB infection - IRIS can still occur if baseline CD4 count >200) 2. High baseline viral load 3. Early ART therapy 4. TB infection - risk of IRIS 40% 5. Rapid improvement after commencing ART

Answer 28

- Start within 2 weeks of HIV diagnosis Only 2 reasons to delay - TB infection, cryptococcal meningitis TB and CD4 <50 - start in 2 weeks of starting TB treatment TB and CD4 count >50 - start in 8 weeks; consider prophylactic steroids if CD4 count <100 and starting ART within 30 days of TB treatment TB meninigitis - wait 8 weeks regardless of CD4 count Cryptococcal meningitis - wait 2 weeks after starting Rx PJP do not need to wait - would be giving everyone steroids regardless PML - only Rx for PML is ART - but can trigger life-threatening IRIS CNS toxo - IRIS with toxo not well described

Answer 29

-Use with protease inhibitors AND elvitegravir (Genvoya) -PK boosters are ritonavir and cobicistat - both inhibit CYP450 CYP450 metabolises majority of the ART drugs - main mechanism of drug interactions *Cobicistat can make serum Cr elevated due to effect on Cr secretion - but does not reduce renal function

Answer 30

Use a regimen containing tenofivir (alafenamide OR disoproxil fumarate) & emtricitabine e.g. Biktarvy or Genvoya If tenofovir or emtricitabine therapy is stopped abruptly - can have acute exacerbation of hepatitis B (Lamivudine can also treat Hep B; however not routinely used for the management of co-infection -> however if abruptly stopped can lead to acute exacerbation of Hep B)

Answer 31

-Presence of HLA-B5701 allele associated with a hypersensitivity reaction which can be fatal -possible association with IHD (hypersensitivity due to HLA-B5701 and CD8+T cells) -Abacavir with HLA-B5701 also associated with DRESS

Answer 32

Can elevate creatinine concentration due to effects on Cr secretion, but do not reduce renal function Dolutegravir (in Tivicay / Triumeq) - associated with anxiety, depression, neural tube defects Raltegravir (in Isentress) - associated with myopathy & rhabdo (but low risk - monitor CK) Elvitegravir needs to be given with cobicistat *low barrier for resistance for raltegravir, but higher comparatively for dolutegravir & elvitegravir Neutral effect on lipids - advantage over protease inhibitors & NNRTIs

Answer 33

Nucleoside / non-nucleoside reverse transcriptase inhibitors bind to viral reverse transcriptase at the deoxynucleotide binding site -> inhibit DNA synthesis Low barrier to resistance Cause **mitochondrial toxicity ** - TDF = older prodrug of tenofovir -TAF & TDF both associated with nephroxicity via damage to proximal tubule (proteinuria, ATN, glycosuria) - but TDF > TAF Check renal function & urine protein every 6 months - reduction in bone density - TDF > TAF TAF - more drug interactions with rifamycins & anticonvulsants, more hyperlipidaemia than TDF.

Answer 34

- Nail dyspigmentation - GI side defects - Lipodystrophy - Increased truncal obesity - Metabolic toxicity

Answer 35

'virenz', 'virapine', 'virine' Do not bind to the deoxynucleotide binding site of viral reverse transcriptase -> lead to altered enzyme conformation -> impaired DNA synthesis **Severe cutaneous adverse reactions ** Hyperlipidaemia - Associated with a risk of SJS and TEN - Nevirapine with HLA B3505 associated with SJS - Nevirapine hypersensitivity reactions include fatal hepatitis / hepatic necrosis (higher risk if higher baseline CD4 count) Efavirenz - CNS toxicity in 1st few weeks (sedation, insomnia, vivid dreams, suicidality), rash (can continue Rx), deranged LFTs, hyperlipidaemia, 1st trimester - neural tube defects, facial clefts, anopthalmia Rilpiverine - QTc prolongation (2nd gen NNRTI) - used as part of 3-drug regimen Delaverdine - rash, headache

Answer 36

Protease inhibitors - high barrier to resistance Integrase inhibitors - some e.g. Dolutegravir have a higher barrier to resistance Nucleoside & non-nucleoside reverse transcriptase inhibitors - low barrier to resistance (e.g. K103N mutation)

Answer 37

'navir' - inhibit cleavage of Gag-Pol polyproteins Require PK boosting - drug interactions due to inhibition of CYP3A4 / CYP450 Class AEs include GI symptoms, CV risk / metabolic side effects including dyslipidaemia, impaired glucose tolerance, lipodystrophy Atazanavir (ATV) - elevated bili; non-adherent will have low bili; lower risk of CVD complications

Answer 38

- major adverse effect of nucleoside reverse transcriptase inhibitors - occurs because NRTIs also bind to human DNA polymerases e.g. mitrochondrial DNA polymerase gamma -> deplete mitochondrial DNA - highest risk NRTIs are stavudine & didanosine (not really used much now) - lamivudine, emtricitabine, abacavir, tenofovir - uncommonly associated with mitochondrial toxicity Presents with myopathy, lactic acidosis, neuropathy, lipoatrophy, pancreatitis

Answer 39

Lipodystrophy - atrophy in face, limbs, buttocks; incr. in central obesity, buffalo hump Nevirapine - SJS with HLA B3505 Abacavir - DRESS with HLA B5701 Zidovudine - nail dyspigmentation Bactrim related reactions

Answer 40

NRTIs, protease inhibitors, integrase inhibitors are effective against both NNRTIs only effective against HIV1

Answer 41

Lamivudine - pancreatitis (rare) Emtricitabine - skin pigmentation (rare) NRTIs are associated with risk of mitochondrial toxicity

Answer 42

- no drug - risk of transmission 25% - IV AZT (zidovudine) alone at delivery -8% - if on ART with VL <50 - risk of transmission <0.09%

Answer 43

Start ART as soon as possible REGARDLESS of CD4 count ART does NOT increase the risk of birth defects Can give ALL HIV drugs in pregnancy Use standard 3 x drug regimen (no role for 2 drug regimens) If VL >1000 or unknown at the time of delivery - recommend

Answer 44

Pre-exposure prophylaxis - 90-99% effective in at risk population if taken consistently Who should have PrEP? - MSM, condomless anal intercourse - Sex workers - recent rectal STI - Must not have HBV or CrCl < 90 - documented HIV negative within 1 week of commencement Regimen - emtricitabine + tenofovir once daily (TRUVADA) Cabetogravir (integrase inhibitor) in the pipeline, half life 8w eeks

Answer 45

- PEP has to be within 72 hrs - 28 day course - success rate 100% if given within 24 hours, 50% people will develop infections if given in 72 hrs. - CD4 T cell HIV reservoir can occur within 24 hours of exposure 2 drug regimen - tenofovir plus emtricitabine OR lamivudine 3 drug regimen - typically 2 NRTIs (pick from above) PLUS integrase inhibitor (dolutegravir or raltevgravir) OR protease inhibitor / rilpivirine Risk of transmission highest in receptive anal intercourse with ejaculation (1:70 from HIV + source); 1:440 for needlestick injury, <1:1000 for mucous membrane & non-intact skin exposure Risk of source having HIV 10% MSM 0.5% IVDU 30% MDM & IVDU <0.003% heterosexuals If undetectable viral load = untransmittable = do NOT require PEP Non-occupational exposure - HIV source with detectable or unknown viral load - 3 drug regimen (SEX all kinds but oral; sharing needles; contact with MM or non-intact skin) Occupational exposure HIV pos with undetectable viral load - consider 2 drug regimen If detectable or unknown viral load - 3 drug regimen

Answer 46

1. Oesophageal candidiasis 2. Streptococcus CAP 3. PJP 4. Toxoplasma encephalitis

Answer 47

1. CD4 count <200 - Bactrim for PJP prophylaxis & toxo prophylaxis 2. CD4 count <100 - fluconazole for fungal / cryptococcal prophylaxis 3. CD4 count <50 - azithromycin 1g weekly for MAC prophylaxis

Answer 48

-PJP caused by Pneumocytis jirovecii (unicellular fungus) - most common opportunistic respiratory infection in AIDs - airborne transmission - usually if CD4 <200 & not on ART. - Start Bactrim prophylaxis when CD4 <200 - thrice weekly vs daily are equally effective - subacute progressive exertional dyspnoea is the presentation in 91% - CXR - fine reticular nodular changes with apical & basal sparing - HRCT - ground glass changes, predominantly apical - PJP commonly found in healthy lungs - positive PCR does not always indicate infection - Sputum PJP PCR - low sensitive 50-90%; 99% specific - bronchial washings - diagnostic yield > 90% - Serum beta D glucan - elevated levels of 1,3, beta D glucan suggestive of invasive fungal infection (PJP or Aspergillus) - LDH usually elevated Bactrim is 1st line Rx - fungus cannot produce its own folate. Does not have ergosterol in its cell wall - therefore cannot use azoles, polyene antifungals or echinocandins Patients with HIV 100x more likely to get SJS from Bactrim Steroids if hypoxia, PAO2 <70, improve mortality Expect clinical improvement in 4-8 days after starting Rx **Best prognostic indicator for survival is level of oxygenation at time of diagnosis** Alternatives to Bactrim - atovaquone, dapsone, pentamidine After 21 day course of Rx - continue at prophylactic dose till undetectable viral load and CD4 count >200 for at least 3 months Do not need to delay ART - just start steroids

Answer 49

Toxoplasma encephalitis Primary CNS lymphoma Tuberculoma

Answer 50

Progressive multifocal leukoencephalopathy HIV encephalopathy CMV encephalitis

Answer 51

CD4 >500 - same as immunocompetent hosts - benign & malignant brain tumours CD4 200-500 - HIV associated cognitive & motor disorders CD4 <200 - CNS mass lesions most common - primary CNS lymphoma Opportunistic infections - toxo, PML, CMV HIV encephalopathy (HAND) Leading DDx for CNS lesion in HIV positive patient with advanced immunosuppression - toxo, primary CNS lymphoma, PML

Answer 52

- most common CNS infection who are not on ART; usually when CD4 <100 - toxoplasma gondii = intracellular parasite - asymptomatic in immunocompetent - > latent infection which can last lifelong - transmission through ingestion of infectious oocytes in cat litter, soil, contaminated feline faeces, undercooked meat from infected animal - parasite remains latent in brain, eyes, myocardium & skeletal muscle - Bactrim prophylaxis for PJP is also effective for toxo - presentation - headache, fever, confusion, focal neurology, seizures MRI - multiple ring enhancing lesions with surrounding oedema + mass effect (single lesions can rarely occur with TE BUT usually solitary large >4cm lesions more suspicious for primary CNS lymphoma) Lesions in posterior fossa more likely TE / infection rather than CNS lymphoma. CNS lymphoma more commonly in corpus callosum, periventricular or periependymal areas CSF toxo PCR positive Management - sulfadiazine + pyrimethamine + leucovorin for 2 weeks (then ART 2 weeks later) Can also use clinda instead of sulfadiazine Can consider a 2 week trial of rx in someone with multiple ring enhancing lesions **should see clinical & radiological improvement in 2 weeks**

Answer 53

EBV Check for EBV DNA in CSF

Answer 54

-risk increases when CD4 count <100 - start fluconazole -presents with subacute / chronic headache, fever, mild confusion / behavioural changes, meningism occurs late -diagnosis on LP - raised opening pressure, lymphocytosis, low glucose, high protein, **India ink stain positive, cryptococcal antigen positive ** Management - therapeutic LP for ICH - high dose amphotericin + flucytosine for 2 weeks (flucytosine has survival benefit) - followed by high dose fluconazole 800mg daily for 8 weeks - secondary prophylaxis till CD4 count >100 and suppressed viral load for 3 months IRIS can occur - fevers, seizures, new CN palsies, new MRI lesions - KEY Is that all cultures negative - other signs can include LNadenopathy, dry cough Mx - NSAIDs, pred

Answer 55

CMV encephalitis / retinitis - AIDS defining illness in advanced immunosuppression MRI - diffuse micronodular encephalitis CMV retinitis is not an indication for Rx unless organ disease Immediate sight-threatening lesion - ARV, IV ganciclovir, intravitreal ganciclovir Small peripheral lesion - ARV, oral valganciclovir

Answer 56

=progressive multifocal leukoencephalopathy - caused by reactivation of JC virus (polyoma virus) - asymptomatic primary infection in childhood - remains latent in kidneys and lymphoid organs - can reactivate when CD4 <200 -> attacks myelin - Presentation - **rapidly progressive neurological deficits including hemiparesis, visual field defects, ataxia, aphasia, cog impairment** - **MRI - **- white matter lesions, multifocal demyelination, NOT contrast enhancing, no mass effect, in periventricular & subcortical white matter - CSF JC virus PCR positive - but negative PCR does not exclude diagnosis

Answer 57

Memory & psychomotor speed impairment Depressive Sx Movement disorders Multiple hyperintense T2 weighted images Non-enhancing Usually symmetrical and less well-demarcated compared to PML

Answer 58

- Disseminated MAC is an AIDS defining illness - associated with advanced immunosuppression CD4 count <50 - presents with systemic Sx - MAC does not present with isolated pulmonary infection in immunosuppressed patients - Management - ethambutol, clarithromycin +/- rifamycin

Answer 59

Co-infection is common - risk of acquiring TB is 9-16x higher if you have HIV Presents with atypical infection if CD4 <200 - typical upper lobe cavitation only seen in 20-30% patients (more common if CD4 count >200) Can instead present atypically with intrathoracic adenopathy, lower lobe opacities, pleural effusions

Answer 60

-Melioidosis is caused by Burkholderia Pseudomallei - gram negative intracellular organism Widely distributed in water & soil - hyperendemic regions in North Australia associated with seasonable peaks / wet season. Majority of cases from SE Asia -Transmission vai percutaneous innoculation tosoil or contaminated H20 Most infections are subclinical Most comon clinical presentation is pneumonia CXR shows discrete, patchy, lobar or multilobar consolidation, necrotising lesions, effusions. - can lead to fibrotic changes mimicking TB in chronic meliodosis Mx - meropenem or ceftazidime

Answer 61

Organisms associated with ART include MAC, TB, CMV, cryptococcus, HHV-8, HSV, HBV

Answer 62

IRIS = immune reconstitution inflammatory syndrome - paradoxical IRIS - previously well-treated infection flares post ART - Unmasking IRIS - previously unrecognised infection becomes apparent after ART Typically occurs within 6 weeks of starting ART **IRIS may develop faster with integrase inhibitors**

Answer 63

Continue ART Treat underlying infection Give steroids for severe symptoms

Answer 64

- Abacavir (NRTI) - possible association with increased risk of MI - Protease inhibitors - have shown to increase CV risk, associated with dyslipidaemia, insulin resistance and lipodystrophy Lopinavir / ritonavir and indinavir - no longer used Atazanavir & darunavir - more commonly used PIs and less CV risk *However, discontinuation of ART is associated with an even higher risk of CV events

Answer 65

Protease inhibitors inhibit CYP3A4 - can result in reduced metabolism of statins & severe rhabdo -**Simvastatin is contraindicated with protease inhibitors** Pravastatin does not interact with PIs Atorvastatin & rosuvastatin only partially metabolised bY CYP3A4 and can be used at reduced dose

Answer 66

-CVD is an important cause of death in HIV patients (incidence of AIDS related death now decreasing since the advent of ART) HIV causes chronic inflammatory state that damages coronary endothelium Traditional CV RFs - smoking, HTN ART related effects HIV decreases HDL, increases LDL and trigs irrespective of HAART HIV positive men - 6 x increased risk of CVD, 2 x increased in women

Answer 67

Anti-LG-1 and Anti-Caspr2 Abs

Answer 68

Mostly T cell mediated - Anti-Hu - SCLC - Anti-Ma-2 - testicular Ca

Answer 69

- CSF HSV PCR - HSV PCR is 96% specific - CSF shows lymphocyte predominance - but can have neutrophilia in early HSV encephalitis, or enterovirus & mumps encephalitis Mildly elevated protein Normal glucose - MRI - asymmetrical temporal inflammation Paraneoplastic encephalitis - limb inflammation EBV, CMV, enteroviruses - changes in cerebellum - EEG- high amplitude slow waves over temproal regions; can aid diagnosis, sensitive but NOT specific

Answer 70

Antibody-mediated autoimmune encephalitis - Abs against NMDA receptor - NMDA important for thought & memory - Strong association with ovarian teratoma in young women - also associated with HSV - Initial symptoms often hallucinations & delusions (may be mistaken for psychiatric illness) - Seizures, dysautonomia, memory loss & movement disorders develop 1-2 weeks later - Anti-NMDA-R Abs in plasma or CSF - CSF much more sensitive - MX - immunosuppression, IVIG, plasma exchange

Answer 71

ADEM = acute disseminated encephalomyelitis - type of autoimmune encephalitis - inflammatory demyelinating encephalopathy - often mimics MS - most common in children - USUALLY PRECEDED BY INFECTION - strong association with measles infection ro vaccination - **anti-MOG Ab in serum = anti-myelin oligodendrocyte glycoprotein** - MRI - diffuse white matter lesions, perivascular inflammation & demyelination - EEG - diffuse slowing - Rx - methylpred AHLE - acute haemorrhagic leuco-encephalopathy - severe & rapidly progressive ADEM - with necrotising vasculitis

Answer 72

Rat - leptospirosis Cat - bartonella Birds - chlamydia psittaci Animal bites - rabies Ticks - Rickettsia

Answer 73

Most common cause in all age groups is Strep pneumoniae 2nd most common cause in <60 yrs - Neisseria meningitidis 2nd most common cause in > 60 yrs - Listeria monocytogenes Other common causes - Haemophilus influenzae, Strep agalactiae

Answer 74

Enteroviruses - coxsackievirus, echovirus etc.

Answer 75

Recurrent (Mollaret's) meningitis - form of benign recurrent lymphocytic meningitis - defined as 3 or more episodes of fever with meningism - that spontaneously resolves within 2-5 days - most common cause is HSV-2 While most HSV encephalitis is HSV1, HSV meningitis is usually HSV2 85% have genital lesions at the time

Answer 76

Healthcare-associated meningitis - occurs soon after cranial or spinal surgery or cranial trauma; OR any time point after insertion of a ventricular shunt Causative organism - MC gram neg bacteria including Pseudomonas 33% - Staph (aureus & coagulase neg) - 18% - Strep pneumoniae, L.monocytogenes & Neisseria meningitidis - only 8% combined Empiric therapy - anti-pseudomonal beta lactam PLUS vancomycin

Answer 77

- Approx. 10% of Strep pneumoniae is penicillin resistant due to the PBP2x protein if MIC <0.125 = susceptible - 2% of Strep pneumoniae has intermediate susceptibility or is resistant to 3rd gen cephalosporins e.g. ceftriaxone If MIC <1 - susceptible MIC 1-2 - intermediate susceptibility MIC >4 - resistant

Answer 78

6-13% resistant to penicillin 90% intermediate susceptibility to penicillin 0% resistant to ceftriaxone

Answer 79

Extremes of age > 50 yrs. ESRF, cirrhosis, diabetes, alcoholism, steroids or other immunosuppressive agents, malignancy, HIV/AIDS, organ transplantation, pregnant, children IV benpen 2.4g Q4H or Bactrim IV 960mg q6h

Answer 80

For patients at risk of ceftriaxone-resistant pneumococcal meningitis - because 2% of Strep pneumoniae is resistant or has intermediate susceptibility to ceftriaxone Patients who should receive vancomycin in addition to ceftriaxone: -gram positive diplococci on gram stain -CSF pneumococcal antigen positive -> BETTER than gram stain & culture for pneumococcus - >95% specific, >85% sensitive -otitis media, sinusitis -recent beta-lactam treatment

Answer 81

- Dexamethasone reduces neurological morbidity & mortality (ESP CN VIII / prevents hearing loss) in patients with pneumococcal meningitis - MUST give BEFORE antibiotics - reduces the inflammatory response from antibiotic mediated bacteriolysis -Reduces CNS inflammation & oedema Continue IV dex 10mg QID for 4 days in pneumococcal meningitis If diagnosed as Neisseria meningitidis meningitis - cease dex as no benefit

Answer 82

Ceftriaxone, benzylpenicillin, flucloxacillin If MRSA suspected or in patients with fulminant endocarditis, replace benpen with vanc In IVDU or hospital acquired - empiric Rx is vanc plus gent Empiric therapy for prosthetic valve or pacemaker lead IE - fluclox, vanc, gent

Answer 83

1. Staph aureus is the most common cause of native & prosthetic valve endocarditis. More aggressive - associated with higher rates of embolisation & stroke, prolonged bacteraemia & higher mortality - 31% 2. Virdians Streptococci - 17% 3. Enterococcus -11% 4. Coagulase neg staph (including staph lugdenesis) - 11% 5. Staph bovis / gallolyticus - 7% 6. Non-HACEK GNs 7. HACEK - haemophilus parainfluenzae, aggregatibacter, cardiobacterium, eikenella, kingella 8. Fungi Prosthetic valve IE within 12 months of valve replacement - CoNS including Staph Lugdenesis is an important cause. CoNS often methicillin resistant After 2 months - causes same as for native ie In IVDU - R) sided IE is due to Staph aureus L) sided IE - pseudomonas, candida, bacillus

Answer 84

- HACEK IE - IV ceftriaxone for 4-6 weeks - Enterococcal IE (vast majority is E.faecalis) - use gent for synergy. Benpen or amoxicillin / ampicillin PLUS gent. if high level aminoglycoside resistance or gent contrainidcated - use ceftriaxone alongside ampicillin - Streptococcal IE - use benpen if penicillin MIC <2 PLUS gent If MIC >2 - vanc plus gent

Answer 85

- Type 1 = polymicrobial; type 2 = monomicrobial

Answer 86

Empiric therapy WITHOUT water exposure - IV taz or mero + IV vanc + IV clinda or lincomycin Empiric therapy WITH water exposure is different bc risk of Aeromonas infection which often produces carbapenemases IV mero plus IV clinda or lincomycin plus IV vanc plus IV cipro IV clinda is a helpful adjunct in patients with necrotising SSTI who have sepsis or shock - reduces production of toxins by GAS (M protein). No benefit in patients with sepsis or shock Directed therapies: GAS - IV benpen plus clinda plus IVIG Role of IVIG controversial Clostridium - benpen plus clinda Community acquired MRSA - IV vanc PLUS clinda

Answer 87

Give tetanus vaccine if >5 yrs. since last or 3rd dose of tetanus toxoid vaccine If 5-10 yrs since last tetanus vaccine but only minor clean wound - nil need for vax Tetanus immunoglobulin indicated if significant wound AND not fully vaccinated (i.e. has not received 3 days OR history unknown)

Answer 88

- bone to probe - visible bone - ESR > 70 - > ulcer duration > 2 weeks - ulcer size > 2cm2 - presence of a "sausage" toe with erythema & non-pitting oedema that obliterates the normal contour of the digit Definitive diagnosis - isolation of bacteria from a bone biopsy

Answer 89

Acute infection - in patients who have not recently had antibiotics - staph aureus or streptococci Chronic diabetic foot infections - often polymicrobial, combination of gram positive & negative aerobic & anaerobic infections Superficial diabetic foot infections (cellulitis, infected ulcer) - often caused by aerobic gram positive cocci - Staph aureus, CoNS, strep pyogenes, strep agalacticae Deep chronically infected ulcers - often polymicrobial - gram positive aerobic cocci - Staph aureus, Strep pyogenes, Strep agalacticae, CoNS - enterococci - enterobactericae - Pseudomonas - often colonises but not necessarily the primary pathogenic organism - Anaerobes MRSA - particularly in patients with previous MRSA infection or colonisation; previous Abx use, recent hospitalisation or living in care facility

Answer 90

1. Mild infection - no evidence of OM, SA - dicloxacillin or fluclox to cover OR cephalexin to cover Staph aureus & beta haemolytic strep - if concerned re MRSA - add clinda, bactrim, linezolid OR cephalexin + bactrim or doxy - if no response within 1 week - broaden cover to include MRSA, anarobes & aerobic GNRs with bactrim + Aug DF OR moxifloxacin OR clinda plus cipro - duration 1-2 weeks 2. Moderate / deep infection - cover Staph aureus, beta haemolytic Strep, aerobic GNRs, anaerobes IV Augmentin OR IV cephazolin plus metronidazole 2-4 weeks if no OM 6 weeks if OM 3. Severe / limb-threatening infection Signs of shock, bacteraemia, systemic toxicity, marked necrosis or gangrene, ulceration of deep tissue, severe cellulitis, **presence of OM or septic arthritis ** - tazocin OR - meropenem OR - Metro & ceft OR ceftazidime OR cipro if penicillin allergy - clinda plus cipro Add vanc, linezolid, daptomycin for MRSA cover

Answer 91

Most commonly - staph aureus, beta haemolytic strep (strep pyogenes, strep dysagalacticae) Gram negative rods - cirrhosis, abdominal wall or groin cellulitis, immunosuppressed, chronic leg ulceration Vibrio vulmiticus - blistering cellulitis caused by eating oysters Pasteurella - dog / cat bites

Answer 92

Yes Indications for IV therapy - evidence of sepsis - comorbidities that increase risk of treatment failure - obesity, chronic venous insufficiency, peripheral vascular disease, heart failure, multiple previous episodes of cellulitis - failure of PO Abx

Answer 93

Caused by mite Sarcoptes scabei Can live outside host for 24-36 hrs Transmission requires prolonged direct skin contact Key Sx is itch - often worse at night Incubation period for primary infection 4-6 weeks Small erythematous papules, burrows - thin red or brown lines Clinical diagnosis usually Often do not need skin biopsy Can do skin scrapings 1st line Rx - topical permethrin 2nd line - oral ivermectin

Answer 94

- caused by gram neg diplococci - Neisseria gonorrhoea - in younger <40 yrs sexually active patients - occurs due to haematogenous / bacteraemic spread of STI - Urethritis / local genitourinary infection precedes disseminated infection - can present as purulent septic arthritis (monoarticular OR oligoarticular) - typically involving distal joints - ankles, wrists, knees OR presents as arthritis -dermatitis syndrome - migratory polyarthralgia without purulent arthritis, dermatitis - painless pustular or vesicopustular lesions - 2-10 on distal extremities AND tenosynovitis - definitive Dx via detection of N.gonorrhoea in blood, synovisual fluid, tissue, skin lesion (NON-mucosal sites) with NAAT testing or culture - mean synovial leukocyte count approx 50,000 - cultures positive in 50% purulent arthritis, less in those with arthritis - dermatitis syndrome Rx - IV ceftriaxone 1g daily for 1-2 days then consider de-escalation

Answer 95

IVDU Extremes of age Immunosuppression Trauma

Answer 96

1. Native septic arthritis - staph aureus - presents typically, but can be polyarticular, may be less painful if taking PO Abx in community - Low virulence organisms e.g. N. gonorrhoea may have less pain - may be missed 2. Periprosthetic joint infection - eary infection <3 months - staph aureus vs staph epidermidis - late infection If caused by low virulence organisms e.g. Staph epidermidis - may be asymptomatic & found incidentally on imaging for chronic mild pain High virulence organisms - staph aureus; present typically

Answer 97

Bone biopsy - surgical sampling - inflamm markers not always up - in low grade infections, compromised hosts or early infection - prone to bone test - imaging - XR changes can take 6/52 to develop, MRI changes can take up to 1 week - MRI may exclude epidural abscess but will not show discitis / osteomyelitis very early on - surgical sampling is gold standard WCC <50,000 - 5% infected 50,000-100,000 - 33% infected >100,000 50% infected presence of sinus tract confirms infection

Answer 98

Myelosuppression - reversible, particularly anaemia & thrombocytopenia. Associated with duration of therapy Serotonin syndrome Taste change LFT derangement Inhibition of mitochondrial protein synthesis can result in optic neuropathy & peripheral neuropathy which may be irreversible; anaemia & lactic acidosis

Answer 99

Inhibition of protein synthesis Binds to 50S ribosomal unit - prevents formation of functional 70S ribosomal complex

Answer 100

Commonly associated Abx: - Fluoroquinolones - use of broad-spectrum quinolones e.g. moxifloxacin is associated with hypervirulent strains e.g. PCR ribotype 027 and 078) -Clindamycin (Lincosamides) -broad spectrum penicillins & combinations -2nd, 3rd, 4th generation cephalosporins -carbapenemes Rarely associated: - Aminoglycosides - Tetracyclines - Tigecycline - metro - vanc - chloramphenicol -nitrofurantoin

Answer 101

RFs for CDI infection - Abx use is most important risk factors -advanced age - VERY important -hospitalisation - severe comorbid illness - cancer chemotherapy - PPI RFs for recurrent CDI - age > 65 yrs. -severe underlying medical disorders -need for ongoing Abx therapy during treatment for CDI - renal impairment - lack of Ab respsonse to CD toxins - especially toxin B RFs for complications from CDI -older age -abnormal blood tests - elevated WCC, low albumin, elevated urea, elevated CRP, abnormal vital signs ** PPI use also associated with increased risk of CDI

Answer 102

First episode mild-mod CDI -metro 400mg PO TDS for 10 days OR vanc 125mg PO QID for 10 days - metro preferred for stewardship although equally effective Severe CDI Any of the following features - leucocytosis, high fever, severe abdominal pain, organ dysfunction, elevation Cr, elevated lactate PO vanc 125mg QID for 10 days IV vanc -> inadequate colonic penetration Evidence to suggest that fidaxomicin is associated with lower rates of recurrence compared to vanc but insufficient data for severe disease IF shock / hypotension, ileus or megacolon Add IV metro 500mg TDS to vanc for 10 days Consider intracolonic vanc - especially if ileus Early surgical referral as poor outcomes after organ dysfunction established **Recent data show lower mortality in patients with severe CDI treated with FMT** Role of bezlotoxumab - monoclonal Ab against CD toxin B not yet defined - NEJM trial 2017 showed lower rate of recurrence compared to placebo First recurrence or refractory disease Recurrence = within 2 months of last infection after resolution of first episode. Refractory = no improvement after 3-4 days therapy PO vanc 125mg QID for 10 days Fidaxomicin 200mg PO BD for 10 days IV vanc cannot be used due to inadequate penetration into lumen Second or subsequent recurrence or ongoing refractory disease - FMT is the preferred therapy for 2nd recurrence or ongoing refractory disease FMT via nasoduodenal tube is superior to vancomycin in patients with recurrent CDI If FMT not available - vanc or fidaxomicin as above **NOTE CDT stool tests can remain positive for >1 month post effective therapy - repeat testing only indicated for symptomatic patients

Answer 103

Surgery: removal of vegetation and repair/replacement of valve Only if: # Heart failure due to valvular dysfunction or perforation - Refractory pulmonary oedema or cardiac shock due to aortic valve or mitral valve dysfunction, obstruction, fistula or shunt - Severe Aortic or mitral regurgitation or dysfunction with poorly compensated haemodynamic function Uncontrolled endocardial infection - Fungal pathogen - Multi-drug resistant pathogen - MRSA, VRE - Paravalvular extension with abscess, fistula or heart block - Persistently positive blood cultures for 6-7 days despite adequate antibiotics - persistent bacteraemia - Partially dehisced prosthetic valve Prevention of systemic embolization Vegetation >10mm when accompanied by >1 embolic event while receiving therapy

Answer 104

Preferred agents: Bactrim 1-2 DS tabs BD Clindamycin 450mg TDS Doxycyline 100mg BD Minocycline - 200mg once, then 100mg daily For empiric therapy Bactrim & Clindamycin would be preferred as also effective against GAS - doxy is not Alternative agents: Linezolid 600mg BD Tedizolid Delafloxacin Omadacycline

Answer 105

Antibiotics of choice: Vancomycin 15-20mg/kg/dose every 8-12 hours Daptomycin 4-6mg once daily Alternate agents - with PO or IV dosing Linezolid Tedizolid Delafloxacin Omadacycline - short acting with IV dosing Ceftaroline - 5th gen cephalosporin Telavancin - synthetic derivative of vancomycin; lipoglycopeptide Abx - long acting with IV dosing Dalbavancin & Oritavancin - synthetic vancomycin derivatives - lipoglycopeptide Abx

Answer 106

-Bactericidal lipopeptide antibiotic - distinct mechanism of action to vancomycin -binds to cell membrane -> causes formation of oligomeric complexes -> creates pores & channels that disrupt thebacterial cell membrane Daptomycin is non-inferior to Vancomycin for staph aureus bacteraemia May be more effective than vancomycin if vancomycin MIC > 1-2 microg/ml Should not be used for MRSA pneumonia as is inactivated by surfactant Only effective for gram positive organisms Cannot penetrate the outer membrane of gram negative bacteria effectively Also effective against VRE Daptomycin susceptibility testing must be conducted before using as therapy as MIC can be influenced by prior exposure to vancomycin Adverse effects Myopathy - weekly CK level Peripheral neuropathy Eosinophilic pneumonia

Answer 107

Prophylaxis As per eTG, antibiotic prophylaxis is only indicated in certain conditions - Mechanical valve/prosthetic material - Previous IE - Uncorrected congenital defects → cyanotic - Rheumatic heart disease and certain settings - Dental - Dermatological if infected - Gastrointestinal if active infection - Respiratory/ENT for tonsils/adenoids or biopsy of the respiratory mucosa - Genitourinary if active infection

Answer 108

C.difficile normally produces toxin A (enterotoxin) and toxin B (cytotoxin) - toxin A increases endothelial permability & apoptosis leading to diarrhoea - toxin B is 10x more potent than toxin A and is a major virulence factor for C.difficile Hypervirulent PCR ribotype 027 - associated with severe outbreaks Produces toxin A & B in increased amounts But also produces a binary toxin - which is not produced by C.difficile normally Also characterised by fluoroquinolone resistance Associated with more severe disease including toxic megacolon, ICU admission, death etc. Increased rates of recurrence and lower rates of cure

Answer 109

HIV RNA viral load - can be detected 9-11 days after exposure - most sensitive & earliest test for acute HIV infection (can detect HIV prior to seroconversion) HIV antibody test - most commonly used for screening - however, can take weeks- months to become positive p24 antigen can detect HIV prior to antibody tests - however, HIV RNA becomes detectable prior to p24 antigen. p24 antigen can also decrease & become undetectable after seroconversion

Answer 110

HIV viral load - predicts progression to AIDS and mortality HIV viral load is a stronger predictor than CD4 count CD38 expression on CD8 cytotoxic T cells is also associated with disease progression

Answer 111

CCR5 delta 32 homozygous mutation inhibits HIV entry into cells due to reduced CCR5 expression on macrophages & T cells -> people with this mutation are strongly resistant to acquiring HIV CCR5 delta 32 heterozygosity is associated with slower progression to AIDS

Answer 112

1. Influenza vaccine - take twice in the year post splenectomy 2. PCV13 (conjugated pneumococcal vaccine) - single dose. After 12 months - 2 x doses of PPV23 five years apart. MUST not take the PPV23 vaccine before the PCV13 vaccine due to risk of vaccine hyperresponsiveness Either 2 weeks before splenectomy or 1 week post 3. MenACWY x 2 doses eight weeks apart (conjugated vaccine) Men B vaccine -> Bexsero - 2x doses 8 weeks apart + 1 x booster 5 years later -> Trumenba - 3 x doses + booster 5 years later 4. Haemophilus influenza B at least once in lifetime

Answer 113

Spleen mediated the IgM response against encapsulated bacteria Without IgM response - CLASSICAL COMPLEMENT pathway is NOT activated - polysaccharide encapsulated bacteria are not opsonised or phagcytosed

Answer 114

Howell-Jolly bodies seen in hyposplenism / asplenia - basophilic bodies that contain nuclear remnants that are normally removed by the spleen

Answer 115

Extremes of age - > 50 yrs OR <5 yrs. Splenectomy due to haematologic conditions - e.g. beta thalassaemia, sickle cell, Hodgkin's lymphoma, ITP, spherocytosis ; associated with higher risk of OPSI than traumatic spleen removal risk of OPSI is highest in first 1-3 years post splenectomy -50% of OPSI occurs in the first 3 yrs. post splenectomy

Answer 116

2 weeks IV minimum 4-6 weeks IV if complicated infection Complicated infection = 1. a positive blood culture result 48 hours after starting appropriate antibiotics 2. fever 72 hours after starting appropriate antibiotics 3. abnormal valvular morphology or evidence of valvular lesions, regurgitation or endocarditis on transthoracic echocardiogram (TTE) or transoesophageal echocardiogram (TOE) 4. no identifiable source of infection or an identifiable source of infection that has not been addressed 5. evidence of metastatic infection (eg vertebral osteomyelitis, endocarditis) 6. intravascular prosthetic material (eg pacemaker, prosthetic cardiac valve, prosthetic arteriovenous graft).

Answer 117

1) Aspergillosis - voriconazole 2) Oral / oesophageal candidiasis - fluconazole. 3) Invasive candidiasis - echinocandins 4) Cryptoccal meningitis - amphotericin B + flucytosine. Consolidation with fluconazole 5) Histoplasmosis - amphotericin B 6) Zygomycosis - amphotericin B

Answer 118

1) Azoles - inhibit 14 alpha demethylase (a cytochrome p450 enzyme) which converts lanosterol to **ergosterol ** -> disrupts **cell membrane integrity ** -> **inhibition of fungal growth ** (i.e. generally fungistatic) 2) Polyenes - bind to **ergosterol** in **cell membrane** -> pore formation -> generally fungicidal 3) Echinocandins - disrupts **fungal cell wall**. Inhibits **beta 1,3, D-glucan synthase which cross-links beta glucans which are polysaccharide polymers that form the fungal cell wall**. Generally **fungicidal** (fungicidal to Candida, fungistatic to Aspergillus)

Answer 119

Invasive candidiasis Invasive aspergillosis **Candida parapsilosis is resistant to caspofungin** **Fungicidal to candida Fungistatic to Aspergillus **

Answer 120

- mild side effects from histamine release - flushing, GI side effects, rash - **Hepatotoxic** - caspofungin Caspofungin metabolised by liver - hydrolysis and N-acetylation & undergoes spontaneous degeration THEREFORE dose adjust in hepatic failure. Anidulafungin is degraded slowly by chemical hydrolysis - does NOT rely on hepatic or renal excretion. - cannot use in pregnancy Only available IV - poor CNS & renal penetration Potential drug interactions - anti-retroviral agents - rifampicin - phenytoin, carbamazepine - cyclosporin, tacrolimus

Answer 121

Azoles are **CYP3A4 inhibitors ** Therefore, can increase levels of: - Warfarin - Statins - Citalopram, escitalopram - tacrolimus, sirolimus, everolimus - fentanyl, methadone, oxycodone - erythromycin - many tyrosine kinase inhibitors - phenytoin

Answer 122

1. Hepatotoxicity 30% patients develop LFT derangement with voriconazole 2. Drug interactions due to CYP3A4 inhibition 3. Inhibition of androgen synthesis -> gynaecomastia, infertility 4. Voriconazole - visual disturbance, photosensitivity

Answer 123

1. Voriconazole - **Aspergillosis, Scedosporium**. Needs tDM. 2. Isavuconazole - broadest spectrum of action; safe in ESRF / CLD. Does not require TDM. PO & IV options. Indications - candida, aspergillus, **zygomycosis ** 3. Posaconazole - can be used as prophylaxis in patients at very high risk of fungal infections (e.g. AML, allogeneic HSCT etc.). Broader spectrum against **candida** & **moulds**. Needs TDM 4. Fluconazole - acute or recurrent **mucucutaneous candidiasis** - vulvovaginal candidiasis where topical therapy has failed - Candidaemia due to susceptibel strains - **not effective against Candida Krusei - complete resistance** - **dose dependent efficacy against Candida glabrata** - Tinea corporis, cruris or pedis resistant to topical therapy - cryptococcus consolidatiion therapy - coccidioidomycosis - histoplasmosis

Answer 124

Polyenes - broadest spectrum antifungal; good CNS & wide tissue penetration Amphotericin B - good for cryptococcal meningitis, resistant bacteraemia Adverse effects - nephrotoxicity - infusion related side effects - fevers, hypotension, rigours, bronchospasm, arthralgias / myalgias, tachycardia, vomiting Liposomal amphotericin - slightly less AEs - HOWEVER, still use echinocandins in preference - echinocandins are non-inferior for invasive candidaemia

Answer 125

Fluconazole - against invasive and mucosal candidiasis Posaconazole - against candidiasis, aspergillus and moulds; indications -AML, graft vs host disease

Answer 126

1. Toxoplasma gondii 2. Nocardia 3. Listeria

Answer 127

HTLV-1 - risk factor for strongyloides hyperinfection Prevalence of HTLV1 is high amongst indigenous people in Central & Northern Australia

Answer 128

Primarily vertical transmission but can also have sexual transmission

Answer 129

- parasitic / helminthic; caused by Strongyloides stercoralis - SE Asia, sub-saharan Africa, Northern Australia, Latin America / Carribean - chronic asymptomatic infection can last decades - main mode of transmission - skin contact with contaminated soil - flaviform larvae penetrate skin -> travel to alveoli via blood / lymphatics -> proliferate in alveoli -> ascend endobronchial tree -> swallowed -> mature into adult worms and burrow in duodenum & jejunum Risk factors for severe Strongyloides infection - defects in cell mediated immunity (HIV, malignancy, ETOH, malnutrition, hypogamma, congenital immunodeficiency) Clinical presentation - acute inflammation, petechiae, itch at site where larvae penetrate skin - evanescent pink tracts as larvae migrate (larva currens) - urticaria around waist in chronic infection - dry cough, dyspnoea, wheeze, haemoptysis. Rarely recurrent fever & pneumonitis. Chronic strongyloides can develop asthma that paradoxically worsens wth steroids. - Duodenitis - leading to upper abdo pain. Chronic enterocolitis & malabsorption from high intestinal worm burden Risk factors for hyperinfection - corticosteroids, TNF inhibitors Disseminated disease - kidneys, brain, liver, meninges Migrating larvae can carry enteric bacteria into blood stream -> sepsis, pneumonia, endocarditis (strep bovis), meningitis **transient eosinophilia seen in majority of chronic infection (not in hyperacute phase)** Stool MCS - higher yield in disseminated / hyperinfection Serology with ELISA has low specificity Treatment is 2 x doses of Ivermectin in immunocompetent or 4 x doses in immunosuppressed Daily ivermectin in hyperinfection Follow up with repeat serology at 3-6 months

Infectious diseases Flashcards

(175 cards)