Infectious diseases Flashcards
CYP3A4 inducers (i.e. will decrease efficacy of other medications)
St John’s Wart
Glucoocorticoids
Carbamazepine
Phenytoin
Phenobarbital
Rifampicin
CYP3A4 inhibitors (will lead to higher levels of the drug)
HIV protease inhibitors - ritonavir, cobicistat
Grapefruit juice
Verapamil, diltizam
? Amiodarone
Clarithyromycin, erythromycin
Itraconazole, ketoconazole
Antibiotic mechanism of action
Mechanisms of antimicrobial resistance in Pseudomonas Aeruginosa
- gram negative aerobic rod
- important cause of VAP - Pseudomonas VAP has highest mortality of all hospital acquired infections
- most common cause of respiratory failure in CF ; Pts with CF often colonised with MDR Pseudomonas with loss of virulence traits
- lipopolysaccharide may play a role in virulence - found in outer membrane of gram negative bacteria & protects from complement activity, triggers cytokine pathways, leads to septic shock
Mechanisms of antimicrobial resistance - both acquired & chromosomally encoded
1. Beta-lactamases
-> AmpC - inducible chromosomal beta-lactamase. Found in ESCAPPM. Hydrolyses extended spectrum (class C) cephalosporins
-> ESBL (class A)
-> Metallo beta-lactamase - less common (class B)
- Reduced permeability - downregulation of outer membrane protein OprD, which is a carbapenem-specific porin -> resistance to carbapenems, particularly imipenem
- Active efflux
- Ability to fomr a biofirm
- Aminoglycoside modifying enzymes
Define MDR
- Multi-drug resistance (MDR): non-susceptible to at least one agent in three or more antibiotic classes
- Extensively drug-resistant (XDR): non-susceptible to at least one agent in all but two or fewer antibiotic classes
Pan-drug resistant: non-susceptible to all agents
What antibiotics are effective in Pseudomonas infections?
- Penicillins
Piperacillin - tazobactam
Ceftazidime - avibactram - Fluoroquinolones - only antibiotic with oral formulation which is reliably active against Pseudomonas. Cipro 750mg PO BD or 400mg IV TDS. Levofloxacin 750mg PO daily. Moxi NOT effective
- 3rd generation cephalosporins
Cefepime, ceftazidime, (cefoperazone), not ceftriaxone - Carbapenems - meropenem
- Aminoglycosides - gentamicin. Do not usually use as monotherapy due to inadequate efficacy
- Polymyxins - colitin & polymyxin B - effective for MDR pseudomonas including metallo beta lactamase producing Pseudomonas
Side effects - renal impairment & neurotoxicity
Combination therapy of beta lactam PLUS aminoglycoside may be helpful in serious infections as empiric therapy but not much data
What are the differences between typable and non-typeable Haemophilus influenzae?
- H. influenzae broadly divided into typeable (typically encapsulated) & non-typeable (typically without capsule)
- typeable A-F are more virulent - type B is most virulent
- non-typeable strains are less virulent
- in places where Hib vaccination uncommon -> leading cause of meningitis & epiglottitis in children & pneumonia in adults
- non-typeable typically causes non-invasive mucosal infections in elderly & children e.g. otitis media & respiratory tract infections (IECOPD, bronchitis, rhinosinusitis, pneumonia).
-rarely non-typable NTHi causes locally invasive genital infections e.g. endometritis, amnionitis, Bartholin gland abscess
-invasive Haemophilus typically occurs in extremes of age & more common with Hib -e.g. meningitis, bacteraemia, epiglottitis etc.
What are the virulence factors associated with haemophilus influenzae?
Most invasive haemophilus infections are due to haemophilus influenza type B -> capsule contains **polyribitol ribose phosphate **which mediates invasion
Other virulence factors
-adhesins - mediate attachment to respiratory mucosa - pilli, fimbriae, high molecular weight factors HMW1, HMW2
-cell wall lipoproteins e.g. lipo-oligosaccharide - impair ciliar function
-biofilm formation
-IgA proteases
**- non-type haemophilus **can survive **intra-cellularly **
- typeable strains have a dense polysaccharide capsule -> renders greater resistance to **complement mediated killing & phagocytosis **
How does the antibody response for typeable vs non-typeable Haemophilus influenzae differ?
Strong antibody response against non-typeable haemophilus influenzae
Ab response is strong & bactericidal with formation of MAC
What is the most common organism identified in pyogenic liver abscess?
Klebsiella (seen in 40%)
What are the virulence factors associated with Klebsiella?
- Capsular serotype - some capsules lack antigens that can be recognised by macrophages / neutrophils - K1, K2, K25
- Hypermucoviscosity - hyperviscous exopolysaccharide web - resists complement mediated serum killing. Associated with magA and rmpA genes - seen disproportionately in Klebsiella forming liver abscess
- Lipopolysaccharide (LPS O side chain can impede C1q or C3b from binding)
- Siderophores - aerobactin binds iron which is an essential growth factors for enterobactericae
- Pili - type 3 fimbrial adhesion protein (MrkD adhesin) plays a key role in virulence of Klebsiella pneumoniae
What proportion of Klebsiella expresses an ESBL?
30% community acquired
44% hospital acquired
Rx meropenem -> step down to cipro
Consider nitrofurantoin / fosfomycin for uncomplicated cystitis
What proportion of E.coli is resistant to penicillin & 3rd gen cephalosporins like ceftriaxone?
12% E.coli produces ESBL - encoded by CTX-M
0.1% E.coli produce a carbapenamase
What features of E.coli make the urinary tract more susceptible to infection?
E.coli causes vast majority of UTIs - up to 95% in people with normal anatomy
P. fimbriae (pyelonephritis associated pilli) is an adhesion that attaches to the D-galactose D-galactose moiety expressed on urothelial cells & RBCs
-also promote persistence of infection by binding to renal basement membrane & Bowman’s capsule, impair ureteric contractility allowing ascend of bacteria from bladder
What are the key features of ETEC?
Enterotoxigenic E.coli = travellers diarrhoea
- incubation period is 1-3 days with rapid onset of Sx
- profuse watery, secretory diarrhoea
- can produce a heat labile (i.e sensitive to heat) and heat stable toxin. Heat labile activates adenylate cyclase -> incr. intracellular caMP -> secretion of chloride
Heat stable activates cGMP -> Cl secretion & inhibition of NaCl absorption
What are the key features of EPEC?
Enteropathogenic E.coli
-profuse watery, secretory diarrhoea & vomiting
-can cause very severe disease & fatal dehydration
-expresses intimin which allows adhesion -> causes re-arrangement of actin in host cell -> “attaching and effacing” effect.
Locus of enterocyte effacement island - 20 protein toxins that are injected directly into the target epithelial cell
What are the differences between enteroaggregative E.coli (EAEC) vs enteroinvasive E.coli (EIEC)?
EAEC - causes both acute & chronic diarrhoea in resource-poor and rich settings. Not invasive - no fever.
EIEC - uncommon; begins as watery diarrhoea & progresses to bloody diarrhoea & frank dysentery WITH FEVER. Closely related to Shigella and causes a colitis similar to shigellosis
What are the features of STEC?
Shiga-toxin producing E.coli
= enterohaemorrhagic E.coli
e.g. O157:H7
- small infectious dose ; large outbreaks
- incubation period around 3 days
- causes bloody diarrhoea without fever
- STEC rarely invades extra-intestinal sites or bloodstream - systemic injury is due to toxinaemia
- key complication is haemolytic uraemic syndrome - complicates STEC infection in about 15% children, less common in adults
- antibiotic treatment for STEC can trigger HUS
- key features - microangiopathic haemolytic anaemia, thrombocytopenia, renal failure
- HUS develops day 7 when diarrhoea is improving
**- decrease in platelet count is the first sign of HUS **
**
If the platelet count is increasing in middle or late phase of illness - risk has passed
STEC patients should be admitted for aggressive fluid resuscitation - aim for haemodilution
Ambler classification of beta lactamases
Are EBSLs plasmid-mediated or chromosomally-encoded?
Plasmid mediated
What is the most common gene encoding ESBL?
CTX-M
What types of bacteria producing ESBLs?
Gram negative aerobic bacteria
What resistance pattern defines ESBL?
- Resistance to 3rd generation cephalosporins e.g. ceftriaxone, ceftazidime
- Resistance to penicillins
- Resistance to aztreonam
- Resistance to 1st & 2nd gen cephalosporins
*Resistance to aminoglycosides & Bactrim often carried on the same plasmid
What are the differences between ESBL & ampC?
- ESBL is plasmid-mediated (constitutively expressed) vs ampC chromsomally encoded & induced
- ampC is sensitive to cefepime - one of the first ways in which lab distinguishes between ESBL & ampC
- ampC is resistant to beta-lactamase inhibitors (except the novel 2nd generation beta lactamase inhibitor avibactam); ESBL is inhibited by beta-lactamase inhibitors, however, this is not clinically useful
- ampC is usually resistant to cefoxitin (2nd gen cephalosporin), but ESBL often appear sensitive in vitro
What are the treatment options for organisms that produce ESBLs?
- Carbapenems
- Ceftazidime - avibactam
- Ceftolozane - tazobactam
- Aminoglycosides e.g. gentamicin, amikacin
- Bactrim
- Fluoroquinolones
What is the preferred treatment for an uncomplicated UTI caused by an ESBL producing organism?
- Nitrofurantoin is 1st line if susceptible & renal funcion ok - eGFR >40
- PO fosfomycin
- PO pivmecillinam
- Bactrim or fluoroquinolones
What are the ESCAPPM organisms?
Enterobacter
Serratia
Citrobacter
Acinetobacter, aeromonas
Proteus (but not Proteus mirabilis)
Pseudomonas
Providencia
Morganella
What pattern of resistance is ampC associated with?
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
What induces expression of ampC?
Which organisms have highly inducible ampC?
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
What are the treatment options for ESCAPPM?
Carbapenems 1st line
Cefepime
Ceftazidime-avibactam
Tazocin - weak inducer of ampC
What are the risk factors for colonisation with carbapenemase producing enterobacterales?
What are the classes of beta-lactamases?
What is the gene encoding colistin resistance?
Colistin resistance identified in 2015
Found in livestock & waterways
Plasmid mediated
Encoded by MCR-1 = mobilised colistin resistance 1
What is avibactam? What is it’s mechanism of action? What organisms is it effective against?
- 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
What are the available therapies for carbapenemase producing organisms?
- 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)
What are the different groups of carbapenemases?
- Class A - Klebsiella pneumonia carbapenemase
- Class B:
New delhi metallo-beta-lactamase
Imipenem resistant Pseudomonas
Verona integron encoded metallo-beta-lactamase - Class D
Oxacillinases - OXA-48 or OXA-181
What are the main side effects of colistic / polymyxin E?
Neurotoxicity & nephrotoxicity (nephrotoxicity is more common)
Neurotoxicity includes opthalmoplegia, paraesthesias, dysphagia, vertigo, respiratory apnoea
What is the mechanism of action of polymyxins?
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
Which organisms are resistant to carbapenems?
Ertapenem has no activity against Pseudomonas
Carbapenems generally not effective against VRE, MRSA, E.faecium, chlamydia, mycoplasma, strenotrophomonas maltophilia
What do the gag, pol & env genes encode?
- Env gene encodes surface proteins - gp120 for surface attachment, gp41 for membrane fusion
- Pol gene encode enzymes - reverse transcriptase, integrase, protease
- Gag gene encodes structural proteins - capsid, matrix, core & nucleocapsid
How does HIV enter cells? Which cells does HIV infect?
-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
Describe the HIV virus lifecycle
-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
How does acute / primary HIV infection present?
= 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
At what point do HIV antibodies become detectable?
At 3-4 weeks post infection
At the time of the primary seroconversion illness
Incubation period - fever in returned traveller
Malaria prophylaxis
CSF characteristics in meningitis
Characteristic features of common causes of bacterial meningitis
Causes of eosinophilic meningitis
> 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
- 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 - Gnathostomiasis - endemic in SE Asia, parts of China & Japan, migratory cutaneous swellings is a common presenting feature
- Baylisascariasis - found in raccoons
Duration of therapy in IE
At what point should a faecal transplant be considered in Clostridium difficile infections?
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
What are some mechanisms by which HIV evades the immune system?
- 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
What are the AIDS-defining illnesses?
- PJP pneumonia
- CMV retinitis
- Toxoplasma encephalitis
- Kaposi sarcoma - HHV-8 - brown lesions on skin & mucosal surfaces
- Candidiasis - throat, oesophagus, bronchus or lungs (but not mouth)
- Cachexia & wasting
- Illnesses associated with herpes virus re-activation - CMV retinitis, EBV-associated hairy leukoplakia on tongue, EBV associated CNS lymphoma
- HIV-associated dementia
- Disseminated mycobacterium avium complex / TB
- Chronic cryptosporidiosis / microsporidiosis
What are the renal manifestations of HIV?
CKD in HIV may be due to HAART or HIV infection
Most commonly focal sclerosing GN - presents with nephrotic range proteinuria and renal impairment
What is DILS and how does it present?
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
What are the diagnostic tests for HIV?
- ELISA testing - very sensitive. Detects the presence of HIV Abs in patient’s serum.
- Western blot - very specific. No longer done.
What is the expected change to CD4 count and HIV viral load after commencing anti-retroviral therapy?
- 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
Main objective of ART by baseline CD4 cell count
What are the risk factors for IRIS after commencing ART in HIV?
- Low baseline CD4 count - usually only if baseline CD4 count <100 (exception is TB infection - IRIS can still occur if baseline CD4 count >200)
- High baseline viral load
- Early ART therapy
- TB infection - risk of IRIS 40%
- Rapid improvement after commencing ART
When should ART be started?
- 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
When should pharmacokinetic boosters be used with antiretroviral therapy?
-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
What ART regimen should be used in patients with HIV plus HBV co-infection?
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)
regi
What are the typical 1st line ART regimens?
What are the adverse effects associated with abacavir (a nucleoside reverse transcriptase inhibitor) used to treat HIV?
-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
What are the adverse effects associated with integrase inhibitors?
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
What are the differences in the adverse effect profile of tenofovir alafenamide vs tenofovir disoproxil fumarate?
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.
Zidovudine (AZT) is used to prevent HIV transmission in pregnancy. What are the side effects?
- Nail dyspigmentation
- GI side defects
- Lipodystrophy
- Increased truncal obesity
- Metabolic toxicity
What is the side effect profile of non-nucleoside reverse transcriptase inhibitors?
‘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
Which classes of anti-retroviral therapy are more commonly associated with resistance?
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)
What are the adverse effects associated with protease inhibitors?
‘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
How CD4 count relate to which opportunistic infections are more likely to occur?
Respiratory infections in HIV
Summary of PJP in HIV
-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
Summary of toxoplasma gondii infections in HIV patients
- 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
How does IRIS present?
Organisms associated with ART include MAC, TB, CMV, cryptococcus, HHV-8, HSV, HBV
What is the empiric therapy for acute meningitis?
Directed therapy for acute bacterial meningitis
What organisms cause necrotising SSTI?
- Type 1 = polymicrobial; type 2 = monomicrobial
Gonoccal septic arthritis summary
- 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
How is a definitive diagnosis of septic arthritis made?
Empiric & directed therapy for septic arthritis
Empiric & targeted antibiotic therapy for osteomyelitis
Which underlying cardiac lesions require Abx prophylaxis when underdoing dental procedures?
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
What does this blood film show?
Howell-Jolly bodies seen in hyposplenism / asplenia
- basophilic bodies that contain nuclear remnants that are normally removed by the spleen
Spectrum of anti-fungal activity
Cutaneous fungal infections
Types of immunosuppressants & associated infections
