ID Flashcards
1
Q
Definition of HIV Treatment failure
A
Viral load persistently >200 copies/ml after 24 weeks of Tx
Confirmed on 2nd test within 3-6 months
Adherence support between measurements
2
Q
• Non-tuberculous mycobacterial (NTM) infection
-insidious, with a chronic cough usually productive of purulent sputum
A
MAC (Mycobacterium Avium Complex)
3
Q
PJP prophylaxis in HIV
A
CD4 count <200
Bactrim daily
4
Q
Toxo prophylaxis in HIV
A
CD4 count <200 and positive serology
Bactrim double strength daily
5
Q
MAC prophylaxis in HIV
A
CD4 <50
Azithromycin 1g weekly or clarithromycin BD
6
Q
Latent TB in HIV
A
TST >5 mm or positive IGRA
Isoniazid with pyridoxine for 9 months
7
Q
HIV Transmission Risk factors for seroconversion in needlesticks
A
o Patient with untreated HIV and high viral load
o Deep injury (Odds ratio 15)
o Device visibly contaminated with patient’s blood (Odds ratio 6.2)
o Needle placement in a vein or artery (Odds Ratio 4.3)
o Terminal Illness in the source patient (Odds ratio 5.6)
8
Q
Timing of PEP and duration
A
Within 1-2 hours of exposure up to 72 hours for most effect, but can be up to one week post exposure
Duration: 4 weeks
9
Q
PEP Regimen
A
Tenofovir DF + Emtricitabine + Dolutegravir
Tenofovir DF + Emtricitabine + Raltegravir
10
Q
Abacavir Hypersensitivity Gene - SJS
A
HLA B5701
11
Q
Dolutegravir in pregnancy?
A
Safe in pregnancy as per WHO study in July 2019
12
Q
Glycoproteins on HIV virus that aid its entry into CD4 T cells and macrophages
A
GP120, GP41, P24 antigen (viral capsid protein - can also be used to test for early detection)
13
Q
Coreceptors on CD4 T cells HIV uses for cell entry
A
CCR5 and CXCR4
14
Q
HIV Incubation period
A
2-4 weeks, up to 10 months
15
Q
HIV Seroconversion Sx
A
Can be asymptomatic
Constitutional symptoms – Fever, fatigue, myalgia
Adenopathy – occasional hepatosplenomegaly
Sore throat
Mucocutaneous ulceration
Generalised rash
Headache – retro-orbital pain
Rarely - opportunistic infection - candidiasis
16
Q
Protective mutation against HIV
A
CCR5 delta 32 mutation - no CCR5 expression on T cell
17
Q
HIV Diagnosis testing
A
- 1st-3rd generation - HIV antibody only
- 4th generation – HIV antibody + HIV p24 antigen (can be detected 1-2 weeks after virus exposure)
- -4th generation >99% sensitivity and specificity for chronic infection
- -Only 80-90% for acute HIV
- -If suspecting acute HIV should also test HIV RNA as routine
18
Q
NRTIs (Names)
A
nucleoside reverse transcriptase inhibitors (NRTIs)
Tenofovir -disoproxil fumarate(TDF) -alafenamide(TAF) Abacavir (ABC) Zidovudine (ZDV/AZT) Emtricitabine (FTC) Lamivudine (3TC)
19
Q
NNRTIs (Names)
A
non-nucleoside reverse transcriptase inhibitor
Efavirenz (EFV)
Nevirapine (NVP)
Rilpivirine
Etravirine
20
Q
PIs (Names)
A
Protease Inhibitors (PIs): “Navirs”
Atazanavir (ATV)
Darunavir
Lopinavir (LPV)
Ritonavir (RTV)
21
Q
ISTIs (Names)
A
Integrase Strand Transfer Inhibitors (ISTIs): “Gravirs”
Raltegravir
Elvitegravir
Dolutegravir
*Bictegravir- licenced 2018
22
Q
Entry Inhibitors
A
Maraviroc
Enfuvirtide
23
Q
HIV Treatment Regimes
A
Usually 2 NRTIs and one other class.
Commonly:
- Raltegravir / tenofovir/emtricitabine
- Dolutegravir /tenofovir/emtricitabine
24
Q
NRTI MOA
A
Mechanism: Inhibit viral replication through competitive binding to reverse transcriptase
25
NRTIs active against Hep B
Tenofovir, lamivudine and emtricitabine
26
NRTI SE
Side effects – historically MITOCHONDRIAL TOXICITY
Peripheral neuropathy, pancreatitis, lipoatrophy and hepatic steatosis
Now uncommon with current NRTIs
27
TAF interaction with rifampicin
reduces level of tenofovir
28
TDF Side effects
Renal failure: Characterised by raised creatinine, proteinuria, glycosuria, hypophosphatemia, and acute tubular necrosis – FANCONI syndrome – proximal renal tubular acidosis. Caution if eGFR <60
Bone loss - decreased bone mineral density - usually stabilizes with continued use
TAF – less toxicity than TDF
29
Abacavir SEs
Hypersensitivity reaction
| May worsen CAD
30
Lamivudine SE
Pancreatitis
31
Emtricitabine SE
skin discolouration usually as hyperpigmentation on palms and/or soles
32
NNRTI MOA
Mechanism: different separate from target site of NRTIs. Bind to a hydrophobic pocket causes a stereochemical change in the protein, which reduces the ability of naturally occurring nucleosides to bind to the active site pocket
33
Efavirenz SE
Potent inducer of hepatic cytochrome P450
CNS toxicity, psychiatric – vivid dreams, confusion, dizziness
QTc prolongation
Elevated hepatic transaminases
34
PIs MOA
Competitively inhibit the cleavage of the Gag-Pol polyproteins in HIV-infected cells
Production of immature virions – non-infectious
35
What should be administered with a PI?
Should be administered with a pharmokinetic booster: Ritonavir or cobicistat
Increases trough plasma drug concentrations, and maximum plasma concentrations
Enables lower and less frequent dosing of the parent drug=decreasing pill burden
36
PI SEs
Nausea, diarrhoea!
Insulin resistance, hyperglycemia, diabetes, hyperlipidemia, lipodystrophy, hepatotoxicity
Interactions: Rifampicin!
37
ISTIs MOA
Integrase enzyme catalyzes the process by which viral DNA is integrated into the genome of the host cell
Target the strand transfer step of viral DNA integration
Prevent or inhibit the binding of the pre-integration complex (PIC) to host cell DNA
38
M184V mutation
HIV mutation often the first to appear.
| REsistance to lamivudine and emtricitabine, BUT hypersusceptibility to TDF/TAF
39
IRIS definition
Collection of inflammatory disorders associated with paradoxical worsening of pre-existing infectious processes following the initiation of antiretroviral therapy (ART) in HIV-infected individuals
40
Crusted Scabies occurs in which populations
AIDS, human T cell lymphotropic virus type 1 (HTLV-1) infection, leprosy, and lymphoma
41
Treatment of Scabies
Topical permethrin and oral ivermectin
42
MOA Permethrin
Topical synthetic pyrethroid agent that impairs function of voltage-gated sodium channels in insects, leading to disruption of neurotransmission
43
Cause of Neurocystiercosis
Taenia solium -Pig tapeworm
44
How does IGRA work
IGRAs are in vitro assays that measure T-cell release of interferon-γ in response to stimulation with highly tuberculosis-specific antigens ESAT-6 and CFP-10 (QuantiFERON-TB Gold In-Tube and T-SPOT TB test).
45
Factors that increase the risk of developing active TB
```
HIV
Immunosuppression
Genetic factors
Smoking
Vit D deficiency
Diabetes/renal impairment
Low BMI
```
46
Which immune cells are involved in forming a TB granuloma
T cells and macrophages
47
Limitations of Tuberculin skin testing
- Responses nor read
- Inaccuracy of measuring induration
- False positives due to sensitisation with related bacteria (BCG vaccine)
48
IGRA Specificity and Sensitivity
- QFT: High Specificity: 96-100%
| - QFT: Sensitivity: 80-85%
49
IGRA limitations
o Does not differentiate between latent and active TB
o May remain positive after successful treatment
o Negative IGRA does not exclude active TB
50
TB in CSF findings
– Lymphocytic pleocytosis, low glucose (DDX Cryptococcal meningitis)
51
o Recommendations for commencing ART in patients with TB
Risk of IRIS
If CD4 < 50 – Early ART (<2 weeks)
If CD4 > 50 then ART by 8 weeks after starting TB therapy
52
Treatment for TB meningitis
HRZM (moxifloxacin better than Ethambutol) 9-12 months
| Dex reduces mortality
53
Standard TB treatment
2HRZE/4HR = 98% Cure
(H) Isoniazid – Most helpful with initial fast multiplying TB
(R)Rifampicin – Usually daily therapy, but can be 3-5 x/wk; most effective on resistors (TB bugs that are hard to kill)
(Z) Pyrazinamide – Slow multiplying TB – works in acidic environments
• If not used then therapy is for 9 months instead of 6 months
(E)Ethambutol
54
Isoniazid SEs
Hepatitis, rash, neuropathy
55
Rifampicin SEs
Drug interactions, hepatitis
56
Pyrazinamide SEs
Hepatitis, skin, joint (gout)
57
Ethambutol SEs
Optic Neuropathy
58
Order of TB drugs that cause the most hepatitis
o Pyrazinamide >Isoniazid >>Rifampicin
59
Mx of TB drugs in setting of derranged LFTs
o If 2-5x normal + asymptomatic = monitor closely
| o If >5x normal or >3 x and symptoms = cease
60
Most common mono-drug resistance in TB?
Isoniazid
61
MDR TB definition
Resistance to INH + RIF +/- any other resistance
62
XDR TB definition
MDR TB + resistance to quinolones and injectables (1 of amikacin, kanamycin, or capreomycin)
63
- fever
- cough/coryzal Sx
- Conjunctivitis
- Koplik's spots (bluish green elevations in buccal mucosa)
- erythematous, maculopapular, blanching rash, which classically begins on the face and spreads cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities
Measles
64
Incubation period for Typhoid
1-2 weeks
65
Clinical features of typhoid
- rising ("stepwise") fever and bacteremia
- "rose spots" (faint salmon-colored macules on the trunk and abdomen)
- fever with headache, arthralgia, myalgia, pharyngitis, and anorexia
- hepatosplenomegaly, intestinal bleeding, and perforation due to ileocecal lymphatic hyperplasia of the Peyer's patches
66
Incubation period of Dengue
3-14 days; Sx typically 4-7 days after transmission
67
Diagnosis of Dengue with warning signs
Diagnosis made as defined in previous column + any one of the following:
- Abdominal pain/tenderness
- Persistent vomiting
- Clinical fluid accumulation (ascites/pleural effusion)
- Mucosal bleeding
- Lethargy/restlessness
- Hepatomegaly >2 cm
- Increase in haematocrit concurrent with rapid decrease in platelet count
68
Diagnosis of Dengue without warning signs
Diagnosis made in the setting of travel to endemic area + fever + 2 of the following:
- N+V
- Rash
- Headache, eye pain, muscle ache, or joint pain
- Leukopenia
- Positive tourniquet test (Tourniquet inflated midway between sys and dys BPs for 5 mins and skin below is examined 1-2 mins post deflation – if 10 or more new petechiae in one sq inch, it is positive
69
Diagnosis of severe Dengue
Diagnosis made as defined in previous column + at least one of the following:
- Severe plasma leakage leading to shock or fluid accumulation with resp distress
- Severe bleeding
- Severe organ involvement (AST or ALT >1000 units/L; Impaired consciousness; organ failure
70
What time period of symptoms should you monitor for warning signs
Day 3-7
71
What is the critical phase of dengue
o Present in Dengue Hemorrhagic fever and Dengue Shock Syndrome, but not Dengue Fever
o Involves systemic plasma leakage, bleeding, shock, and organ impairment
o Lasts for 24-48 hours
o Initially have adequate circulation, but then compensation occurs with pulse pressure narrowing
o Moderate to severe thrombocytopenia may occur with a nadir of platelets <20, which improves rapidly in the recovery phase
72
What is a clinical feature of entering the convalescent phase Dengue
“WHITE ISLANDS IN THE SEA OF RED”
73
Diagnosis of Dengue
Reverse transcriptase PCR (positive in first 5 days of illness)
NS1 (Viral antigen nonstructural protein 1) - positive in first 5 days
Dengue Serology - IgM dectected as early as 4 days after onset
- Primary: IgG up in 7 days
- Secondary: IgG in 4 days
74
Fever in Returned Traveller Incubation <10 Days
```
Dengue
Influenza
Yellow fever
Chikungunya
Plague
Paratyphoid fevers
Legionella
```
75
Fever in Returned Traveller Incubation up to 21 days
```
Malaria
Viral haemorrhagic fever
Q fever
African trypanosomiasis
Typhoid fever
Brucellosis
Leptospirosis
Relapsing Fever
```
76
Fever in Returned Traveller Incubation > 21 days
```
Malaria
Viral hepatitis
HIV
Rabies
Visceral leishmaniasis
Amoebic liver abscess
Filariasis
TB
Q Fever
Acute schistosomiasis
```
77
Mx of Nec Fasc
Carbapenem + agents against MRSA + Clindamycin
78
Role of Clindamycin in Nec Fasc
antitoxin and other effects against toxin-elaborating strains of streptococci and staphylococci
79
Septic arthritis, tenosynovitis, vesicular pustules, negative synovial fluid culture and stain
Disseminated gonnococcal infection
80
Ix of Orbital cellulitis
Blood cultures
| CT of sinuses
81
Mx of orbital cellulitis
3-14 days IVABx
-Cefotaxime OR Ceftriaxone +Fluclox
Followed by 10 day PO tail of Aug DF
Surgical Drainage if abscess found
82
Features of C. Diff suggesting need for early surgical referral
o Hypotension
o Fever ≥ 38.5
o Ileus or significant abdominal distension
o Peritonitis or significant abdominal tenderness
o Altered mental status
o WBC > 20 cells/mL
o Lactate > 2.2 mmol/L
o ICU admission
o End organ failure
o Failure to improve after 3-5 days of maximal medical therapy
83
Mx of C. Diff
Mild to Mod: PO Metro TDS for 10 days
Severe: PO Vanc QID for 10 days/Fidaxomicin
Complicated: PO Vanc and IV Metro
84
When to retest stool for C. Diff
IF needed to test, must be >6 weeks post treatment
85
Recurrent C Diff Mx
FMT if recurred 3x despite adequate treatment
86
Causes of infective bloody Diarrhea
```
SEECSY = Bloody Diarrhea Doesn't Sound Sexy
S=Salmonella
E=E Coli EHEC, ETEC
E = Entamoeba
C = Campylobacter
S=Shigella
Y=Yersinia
```
87
Which malria screening test allows for accurate speciation?
Thick blood films check for parasite burden, thin films allow for speciation
88
CAuse of painful genital ulcers vs painless
painful: herpes much more common than chancroid
painless: syphilis more common than lymphogranuloma venereum
89
Aciclovir and Ganciclovir MOA
inhibits the viral DNA polymerase
90
Amantadine MOA and Indication
Inhibits uncoating (M2 protein) of virus in cell. Also releases dopamine from nerve endings
Influenza, Parkinson's
91
HIV Patient
CT: usually single or multiple ring enhancing lesions, mass effect may be seen
Thallium SPECT negative
Toxoplasmosis
92
Tx of Toxoplasmosis
sulfadiazine and pyrimethamine
93
HIV Patient
CT: single or multiple homogenous enhancing lesions
Thallium Spect Postive
CNS lymphoma
94
typically prodrome: fever, malaise
| causes pyrexia of unknown origin, atypical pneumonia, endocarditis (culture-negative)
Q Fever
95
Coxiella burnetii, a rickettsia
Q fever
96
Bartonella henselae
Cat Scratch Disease
97
S. pneumoniae
| Gram stain
gram positive diplococci/chain
98
E. coli
| Gram Stain
gram negative bacilli
99
H. influenzae
| Gram Stain
gram negative coccobacilli
100
L. monocytogenes
| Gram stain
gram positive rod
101
Neisseria meningitis
| Gram stain
gram negative diplococci
102
Fluctuating temperatures, transient arthralgia and myalgia, hyperhidrosis with a 'wet hay' smell. The clue in the history is his exposure to unpasteurised cheese.
Brucellosis
103
Cutaneous leishmaniasis
- spread by sand flies
| - caused by Leishmania tropica or Leishmania mexicana
104
Mucocutaneous leishmaniasis
caused by Leishmania braziliensis
| skin lesions may spread to involve mucosae of nose, pharynx etc
105
Visceral leishmaniasis (kala-azar)
mostly caused by Leishmania donovani
occurs in the Mediterranean, Asia, South America, Africa
fever, sweats, rigors
massive splenomegaly. hepatomegaly
poor appetite*, weight loss
grey skin - 'kala-azar' means black sickness
pancytopaenia secondary to hypersplenism
the gold standard for diagnosis is bone marrow or splenic aspirate
106
Jarisch-Herxheimer reaction
the Jarisch-Herxheimer reaction is sometimes seen following treatment of syphillus
- fever, rash, tachycardia after the first dose of antibiotic
- in contrast to anaphylaxis, there is no wheeze or hypotension
- it is thought to be due to the release of endotoxins following bacterial death and
- typically occurs within a few hours of treatment
- No treatment is needed other than antipyretics if required
107
BCG vaccine
live
108
MMR vaccine
live
109
yellow fever vaccine
live
110
Hepatitis A vaccine
Inactivated
111
Influenza vaccine
inactivated
112
DTP vaccine
toxoid (inactivated)
113
Yellow Fever
classic description involves sudden onset of high fever, rigors, nausea & vomiting. Bradycardia may develop. A brief remission is followed by jaundice, haematemesis, oliguria
Councilman bodies (inclusion bodies) may be seen in the hepatocytes
114
Kaposis sarcoma
caused by HHV-8 (human herpes virus 8)
presents as purple papules or plaques on the skin or mucosa (e.g. gastrointestinal and respiratory tract)
skin lesions may later ulcerate
respiratory involvement may cause massive haemoptysis and pleural effusion
radiotherapy + resection
115
PJP Tx
co-trimoxazole
IV pentamidine in severe cases
aerosolized pentamidine is an alternative treatment for Pneumocystis jiroveci pneumonia but is less effective with a risk of pneumothorax
steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)
116
3 EBV: associated malignancies:
Burkitt's lymphoma
Hodgkin's lymphoma
nasopharyngeal carcinoma
117
Leptospirosis
-Infected rat urine
```
Features
fever
flu-like symptoms
renal failure (seen in 50% of patients)
jaundice
subconjunctival haemorrhage
headache, may herald the onset of meningitis
```
Mx - Benpen or doxy
118
Schistosomiasis
worms deposit egg clusters (pseudopapillomas) in the bladder causinginflammation
Features
- Swimmer's itch in patients coming back from Africa
- Urinary freq
- Haematuria
- Bladder calcification
Tx - Single dose praziquantel
Risk factor for SCC of bladder
Alternative one causes hepatosplenomegaly due to portal congestion
119
What percent of pf penicillin skin test positive patients lose skin testing positivity to penicillin at 5 years
50%
120
What proportion of "penicillin allergic" patients are negative on pencillin skin testing
>80%
121
What is a Type A ADR
Predictable
Dose Dependent
Non-immune mediated
122
What is a Type B ADR
Unpredictable
Less dose dependent
Immune mediated
-T cell (delayed)/IgE (immediate)
123
Mechanism behind Vancomycin Red Man Syndrome
Non IgE related mast cell activation
| Anaphylactoid response
124
Mast cell receptor associated with non IgE m mast cell activation with ABx use
MRGPRX2
Most common drugs:
Cipro, Clinda, vanc
125
What is the major cause of cross-reactivity between penicillins and cephalosporins
R1 side chain
126
Rate of cross reactivity of penicillin and cephalopsorins
<2%
127
What is the cross reactivity if patient is known to have a cephazolin anaphylaxis
Cephazolin does not have any shared side chains
| -NO other cross reactivity with other ABx
128
Allergy with anaphylaxis to Ampicillin or Cephalexin
Shared R1 side chain
| CROSS REACT
129
Features of low risk beta lactam allergy that oral challenge can be given to
Unknown rxn >10 years
Type A ADR
MPE >10 years or benign childhood rash
130
What is the negative predictive value of penicillin allergy testing in patients with a history of immediate penicillin hypersensitivity
>95%
131
Gold standard testing for immediate penicillin allergy
skin prick testing/Intradermal testing
-This is less sensitive for cephalosporins
132
Mechanisms for Abx resistance
1. ABx inactivation
2. Alteration of antibiotic target sites
3. Decreased ABx permeability of the cell wall
4. Active ABx efflux from bacteria
133
Incubation period <10 days
```
Dengue
Influenza
Yellow fever
Chikungunya
Paratyphoid fevers
Legionella
```
134
Incubation period up to 21 days
```
Malaria
Viral hemorrhagic fever
Rickettsial disease/Qfever
African Trypanosomiasis
Typhoid fever
Brucellosis
Leptospirosis
Relapsing fever
```
135
Incubation period >21 days
```
Malaria
Viral hepatitis
HIV
Rabies
Leishmaniasis
TB
Q fever
Schisosomiasis
```
136
First line treatment of uncomplicated malaria
artemether-lumefantrine(Riamet)
- 4 tabs BD for 3 days
- Take with fatty food for absorption
137
Second Line treatment for uncomplicated malaria
atovaquone-proguanil(Malarone™)
| -Slower parasite clearance, and increased treatment failure compared to first line
138
Indications for IV therapy and/or ICU monitoring in severe malaria
```
Unable to tolerate oral therapy
Altered consciousness
>2% parasitemia
Jaundice, oliguria, severe anemia, hypoglycemia, acidosis, ARDS
```
139
Side effects of IV Artesunate
Cerebellar ataxia, abdo pain/diarr, ALT, delayed haemolysis
Less mortality with Artesunate compared to quinine
140
Side effects of quinine
hypoglycemia, hearing loss, ↑ QT, diarrhea
141
Cause of artesunate resistance in SE asia
single point mutation in the “propeller “region of P falciparum kelchprotein on chromosome 13
142
Role for Primaquine in malaria
Eliminates liver forms of P vivax & ovale
Need G6PD screen
143
Doxycycline Side effects
Photosensitivity (10%): avoid prolonged sun exposure
GIT upset: nausea, vomiting, diarrhoea, oesophageal ulcer
Vaginal thrush, OCP ineffective
144
Mefloquine SEs
Resistance areas in SE asia
Significant SE’s: GI, cardiac, neurological
Psychotic episodes/seizures: <1 in 10,000
145
Tx of Traveller's Diarrhea
Azithro 1 gram stat or 500 mg PO daily for 3 days
| Alt: Ciprofloxacin
146
Tx of Giardia
Tinidazole 2g oral stat OR Metro 400 mg PO TDS for 7 days
147
Zika and timing of contraception/pregnancy
3 or 6 months for men
8 weeks for women
Cx: microcephaly
148
Zika Manifestatons
Fevers, rash, small joint arthritis, conjunctivitis, resolves in one week
149
Warning signs of Dengue
```
Abdo pain or tenderness
Persistent vomiting
Clinical fluid accumulation
Mucosal bleeding
Letheragy, restlessness
Liver enlargement >2cm
Increase in HCT with decerease in platelets
```
150
5 phases of classic dengue fever
1st phase
-Abrupt onset of fevers (39 to 40˚C) for 2 -3 days
-Severe back pain, HA, retro-orbital pain
-Arthralgias, myalgias, transitory maculopapular rash (70-75%)
-Metallic taste
2nd phase: D 3-6; A/N/V/D, lymphadenopathy
3rd phase: Defervescence for 1-2 days
4th phase: Fever recrudescence, morbilliform rash, skin desquamation
5th phase: Convalescence with prolonged lethargy
151
4 Criteria for Dx of Dengue Hemorrhagic fever
Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (≤100,000/mm3)
Objective evidence of “leaky capillaries:”
-Elevated hematocrit(20% or more over baseline)
-Low albumin
-Pleural or other effusions
152
Criteria for Dx of Dengue shock syndrome
4 criteria for DHF plus evidence of circulatory failure (rapid weak pulse, hypotension)
153
Features of Ebola
```
Fever, myalgias, weakness,
vomiting diarrhoea,abdopain,
rash, easy bruising, conjunctival injection
Huge fluid shifts and electrolyte disturbances
```
154
Chikungunya
```
Alphavirus
Spread by aedes aegypti and albopictus mosquitos
Large outbreaks in India, Malaysia, Indian ocean islands, the Caribbean
Incubation 2-4 days ( range 1-14)
Fevers, arthralgias, rash, myalgia
Diagnosis –serology and alphavirus PCR
```
155
Causes of early prosthetic valve endocarditis
```
Coag neg staph
MSSA
MRSA
Corynebacterium
Propionibacterium
```
156
Strep Veridans IE Tx
- 2weeks IV Penicillin and Gent OR 4 weeks IV pencillin
| - Ceftriaxone substitute if penicillin allergy
157
Enterococcal IE Tx
4-6 weeks IV penicillin/ampicillin + Gent
158
Staph IE Tx
4-6 weeks IV Fluclox/1st gen cephalosporin
MRSSA: Vanc 4-6 weeks +/- Rifampcin or fusidic acid for prosthetic valves
159
Uncomplicated TV endocarditis
2 weeks IV fluclox and gent
If complicated: 4 weeks
160
Tx of culture negative IE
Ceft and Gent
161
Indications for surgery in IE
Heart failure
Paravalvular extension (abscess, fistula, heart block)
Uncontrolled infection (Bacteraemia >10 days)
Recurrent embolic events
162
Tx of Orbital Cellulitis
1. Cefotaxime IV 2 g TDS
2. Combination of: Ceftriaxone IV 2 g Daily + Flucloxacillin IV 2 g QID
Must be followed by Oral tail of Augmentin DF PO 875/125 mg BD for 10 days
163
Which ABx has been shown to reduce exacerbations in bronchiectasis with known colonisation with pseudomonas
Azithro
164
ESCAPPM intrinsic resistance
Inducible 3rd gen cephalosporin resistance
"ESBL"
AmpC gene in the chromosomes
-Cefepime still effective against AmpC organisms
165
What other resistance is usually passed along with ESBL genes
Fluroquinolone resistance
166
CRE Mx
High dose Meropenem w/ extended infusions (if MIC <8)
+Aminoglycloside OR Colistin
+Fosfomycin or Tigecycline
Other Drugs:
Ceftazadime-Avibactam (only for KPC)
Ceftolozone-Tazobactam
167
Ceftolozane-tazobactam
Main role in MDR pseudomonas
| -Inhibits PBPs more specific to pseudomonas
168
Staph Aureus methicillin resistance gene
mecA
| encodes the low-affinity pencillin-binding protein 2A (PBP2A)
169
Pathophys for rheumatic fever
Autoimmune response due to molecular mimicry between M-proteins of strept pyogenes (group A beta-haemolytic strept) and cardiac myosin/laminin
Type II hypersensitivity reaction
170
Modified Jones Critieria for Rheumatic fever
Dx – Modified Jones criteria (>2 major, 1 major + >2 minor)
- Carditis= cardiomegaly, new murmur, CCF, percarditis, valvular disease
- Migratory polyarthritis – temporary migrating arthritis usually of large joints; beings in legs and migrates upwards
- Subcutaneous nodules
- Erythema marginatum – pink/red, non-puritic rash involving trunks/arms; snake-like ring with clearing in middle, spares face
- Sydenham’s chorea
Minor
- Fever, arthralgia, previous episodes of RF
- Incr ESR/CRP, leukocytosis, heart block on ECG, evidence of streptococal infection (ASOT titre, DNAse)
171
Secondary prophylaxis against streptococcus pyogenes (Rheumatic Fever)
Benzathine pencilllin 900mg IM; every 3 or 4 weeks OR
Phenoxymethylpenicillin 250mg orally, BD
Prophylaxis should be considered
- For a minimum of 10 years after the most recent episode of acute rheumatic fever
- At least until 21 years in patients without carditis or clinically evident valve disease
- Until 35 years of age in patients with residual moderate valve disease
- Until 40 years of age or life in patients with severe residual valve disease and in those who have had valve surgery
172
Enteroccus Faecium mutation that leads to ampicillin and vancomycin resistance
Amp - mutations in PBP5 (penicillin-binding protein)
Vancomycin – replacement of pepidoglycan component d-alanaine with d-lactate or d-serine
173
Mechanism behind VRE
Vancomycin inhibits by binding to D-alanyla-D-alanaine – inhibits cell wall synthesis
Mutation in D-Ala-D-Ala = resistance
174
Van A
high resistance to vancomycin and teicoplanin
175
Van B
teicoplanin still generally effective; most common form of enterococci resistance
176
Van C
low resistance to vancomycin; sensitive to teicoplanin
177
HIV: OI with CD4 200-500
HSV
Pneumococcal pneumonia
oral candida
TB
178
HIV: OI with CD4 50-200
```
PJP
CNS Toxo
Cryptococcus
Kaposis sarcoma
Non Hodgkins lymphoma
Primary CNS Lymphoma
```
179
HIV: OI with CD4 <50
MAC
CMV retinitis
Cryptosporidiosis
180
Cat Bites: Pastuerella Multocida
Resistance to usual cellulitis Tx (pencillin and cephazolin)
| -Tx: Tazocin or ceftriaxone
181
MRSA mechanism of resistance
modified penicillin binding protein - altered site of beta lactam binding (mecA gene for PBP2a)
-Cant be overcome by beta lactamase inhibitor
182
Panton Valentine Leucocidin
PVL is a pore forming necrotising exotoxin that causes leucocyte destruction and tissue necrosis
-PResent in a majority of nmMRSA
183
Linezolid MOA and SE
Bacterostatic
Inhibits protein synthesis
Binds 50S ribosomal subunit
SE: reversible bone marrow depression with prolonged use, irreversible neuropathy, optic neuropathy,
Serotonin syndrome
184
Daptomycin MOA and SE
cyclic lipopeptide bactericidal antibiotic that causes depolarisation of the bacterial cell membrane
SE: myopathy, peripheral neuropathy, eosinophilic pneumonia
Monitor CK
185
Tigecycline MOA and SE
minocycline derivative
Protein synthesis inhibitor; binding at 30s ribosomal subunit - bacteriostatic
High Vd and eliminated via biliary tree not urine
SE: higher risk of Tx failure and increased death rates (last resort)
186
Ceftaroline/Ceftobiprole
5th gen cephalosporin
For MRSA, VRE (faecalis)
SE:Eosinophilic pneumonia rarely
187
Vancomycin MOA and SE
Inhibits synthesis of bacterial cell wall by binding to D-ala D-ala terminus of side chain preventing cross linking
SE: nephrotixicity, ototoxicity, Red man syndrome, neutropenia, thrombocytopenia, rash
188
Teicoplanin MOA and AE
Similar to Vancomycin
SE: nephrotoxicity, ototoxicity
189
MEchanism behind pneumococcal penicillin resistance
alteration in PBP
- No role for beta lactamase inhibitors for this
- MAy be overcome with high doses dependent on MIC
190
Types of CRE
```
KPC (US)
NDM(Aus/Nz/India)
OXA-48 (Turkey)
VIM
IMP
```
191
What is the best prognostic indicator for survival in PJP
Level of oxygenation at diagnosis
| -PaO2 <70 mmHg - Add pred (improves mortality)
192
CNS Toxoplasmosis in HIV
CD4 usually <100
PResentation: fever, headache, mental state change, neuro deficits, seizure
Dx: IgG, multiple ring enhancing lesions
Tx: pyrimethamine/sulfasiazine OR Pyrimethamine/Clinda and Bactrim; Dexamethasone for mass effect
If not improved in 2 weeks on CT - Bx for ?CNS lymphoma
193
Empical Tx for bacterial meningitis
IV 2g Ceftriaxone BD
IV 10 mg Dexamethasone Q6H
+Vanc if pneumococcal risk
+Benpen 2.4g IV Q4H if listeria risk
194
Risk Risk criteria for TOE in ?IE
Community acquired bacteraemia
IVDU
High risk cardiac condition
Indeterminate or positive TTE
195
Common Culture negative endocarditis bugs
```
Bartonella
Coxiella burnetti
Brucella
LEgionella
Tropheryma whipplei
```
196
Specific Streptococcal IE Tx
```
IV Benpen 1.8 Q4H for 4 weeks
OR
IV Ceftriaxone 2g daily for 4 weeks
OR
IV Benpen + Gent for 2 weeks
```
197
Specific Enterococcal IE Tx
IV Benpen 2.4g Q4H + gent for 4-6 weeks
OR
IV Vanc + Gent for 4-6 weeks
If Gent contraindicated: Benpen and Ceftriaxone for 6 weeks
198
Specific HACEK IE Tx
Ceftriaxone +/- Gent for 4-6 weeks
199
Prosthetic valve and staph aureus IE Tx
Fluclox + Rifampicin + Gent (for first 2 weeks) for a total of 6 weeks
200
High risk heart conditions needing IE prophylaxis for high risk procedures
- Prosthetic heart valve
- Rheumatic valve disease
- Previous IE
- Unrepaired cyanotic congenital heart disease (or repaired in last 6 months)
201
High risk procedures needing IE prophylaxis for high risk groups
- Dental procedure that manipulates gingival tissues or perforates mucosa
- Tonsillectomy or adenoidectomy
- Surgery at site of established infection
202
ABx choice for IE prophylaxis
Amoxycillin 2 gram - PO then one hour prior - IV just before procedure
Penicillin allergy or penicillin/cephalosporin taken in the last month:
-Clindamycin or clarithromycin
203
CURB 65
```
Confusion
Urea > 7 mmol/L
RR >30
BP <90 or dia <60
Age >65
```
204
L-Amphotericin B MOA
Intercalated between phopholipid layer
Binds to ergosterols in the cell membrane.
Increased Membrane permeability and
Pore formation
Good CSF penetration
205
SE of L-AmB
```
Nephrotoxicity
Infusion reaction (fevers, chills, hypotension, bronchospasm, myalgias, N+V, tachycardia
```
206
Indications for L-AmB
```
Cryptococcal meningitis
Alt to Voriconazole for IA
Invasive candidaemia
Zygomycosis
Fusariosis
Empiric fungal therapy
```
207
MOA of Tiazoles
Inhibit the C-14alpha demethylase required for fungal cell membrane (ergosterol) synthesis
208
MOA of Echinocandins (Fungins)
Inhibits synthesis of beta-1,3-D-glucan this inhibiting cell wall synthesis
209
MOA of Flucytosine
converted by cytosine deaminase to fluorouracil in fungal cells; after phosphorylation fluorouracil inhibits fungal DNA synthesis and is also incorporated into fungal RNA, affecting protein synthesis.
210
First line treatment for invasive candidiasis
Echinocandin (caspofungin)
-If confirmed sensitivities can switch to azole
Micafungin better for C.auris and obese patients
211
SE of echinocandins
Relatively well tolerated
N+V
Some LFT derrangement
Unclear urianry penetrance
212
Indication for posaconazole
o Prophylaxis in AML and MDs undergoing intensive induction-remission chemotherapy and post HSCT or GVHD
213
Voriconazole SEs
o Elevation of LFTs
o Photosensitive rash
o Transient dose related visual disturbances (increased brightness and blurred vision)
o IV formulation – exacerbates pre-existing renal disease (relative contraindication if eGFR<50ml/min
214
Which triazoles need monitoring
Vori and Posa
215
First line treatment for invasive aspergillosis
Voriconazole (Excellent CNS penetration)
216
Drugs that interact with Echinocandins
* Cyclosporin A
* Tacrolimus
* Antiretroviral agents
* Phenytoin
* Carbamazepine
* Rifampicin
217
Indication for Flucytosine
Used with amphotericin for synergy in cryptococcal infn (esp meningitis)
218
Tx of oesophageal candidiasis
Fluconazole
| If resistant and intolerant of L-AmB, then caspofungin
219
New Anti CMV treatment in patients with HSCT - can be used for prophylaxis
Letermovir and Maribavir
- Bind to CMV terminase complex rather than the polymerase (like ganciclovir)
- Very specific to CMV virus
- Minimal myelotoxicity
220
Mx of Toxic Shock Syndrome
Clindamycin + vancomycin as empirical cover
| -IVIG may be good adjunctive
221
Most common cause of Traveller's diarrhea
Enterotoxigenic (ETEC)
| E. Coli
222
Most common cause of community acquired inflammatory enteritis
Campylobacter jejuni
223
Risk factors for salmonellosis
Sickle cell disease, malaria, schistosomiasis, bartonellosis, pernicious anaemia
224
Botulinum toxin target
= blocks acetylcholine release
225
Tetanus toxin MOA
= travels to CNS by retrograde axonal transport
Inteferes with GABA transmission so that alpha-motor neurons are no longer under inhibitory control
226
Cholera MOA
Chlorea toxin = causes persistent activation of adenylate cyclase
Increase in cAMP in intestinal mucosa and leads to increased Cl secretion and decreased Na absorption which leads to diarrhoea
227
Antigenic shift
Antigenic shift occurs in major changes
| -causes pandemics or epidemics
228
Antigenic Drift
Antigenic drift – minor, point mutations occur leading to local outbreaks
229
Rheumatic fever Pathophysiology
Autoimmune response due to molecular mimicry between M-proteins of strept pyogenes (group A beta-haemolytic strept) and cardiac myosin/laminin
-Type II hypersensitivity reaction
230
Jones Criteria for Rheumatic fever
Dx – Modified Jones criteria (>2 major, 1 major + >2 minor)
- Carditis= cardiomegaly, new murmur, CCF, percarditis, valvular disease
- Migratory polyarthritis – temporary migrating arthritis usually of large joints; beings in legs and migrates upwards
Subcutaneous nodules
Erythema marginatum – pink/red, non-puritic rash involving trunks/arms; snake-like ring with clearing in middle, spares face
Sydenham’s chorea
Minor
Fever, arthralgia, previous episodes of RF
Incr ESR/CRP, leukocytosis, heart block on ECG, evidence of streptococal infection (ASOT titre, DNAse)
231
Scarlet Fever pathophysiology
Diffuse erythematous eruption; due to delayed type skin reactivity to pyogenic exotoxin (erythrogenic toxin)
232
Intracellular bacteria
```
Listeria
Mycobacterium
Brucella
Rickettsia
Chlamydia
```
233
Clostridium botulinum presentation
Symmetric descending paralysis
| Normal reflexes
234
Most common cause of traveller's diarrhea
ETEC
235
Most common cause of community acquired diarrhea
Camplyobacter jejuni
236
SE Flucloxacillin
cholestatic jaundice (especially older patients on prolonged therapy)
237
Which of the cephalosporins is the only one excreted via biliary tree rather than kidneys
Ceftriaxone
238
SE Vancomycin
Red man Syndrome
-Mx: Stop infusion, antihistamine, start infusion slower
Nephrotoxicity
Ototoxicity
Neutropenia
239
SE Coistin
Nephrotoxicity
Neurotoxicity
Hypersensitivity
240
50S ribosomal subunit inhibitors
```
Macrolides
Lincosamides = clindamycin
Fusidic acid
Chloramphenicol
Linezolid
```
241
30S subunit inhibitors
Aminoglycosides
Tetracycline
Tigecycline
242
Which ABx class worsens Myasthenia gravis
Quinolones
243
SE of Quinolones
Tendon rupture/tendonitis
-Risk factors – concomitant steroid use, advanced age, renal impairment, prolonged therapy
QT prolongation
Photosensitivity
CNS toxicity – nightmares, dizziness, confusion
244
SE of Metronidazole
Metallic taste
Peripheral neuropathy
Seizures if prolonged large doses
Avoid in pregnancy/lactation
245
Side effects of Bactrim
Hypersenstivity rash
Bone marrow suppression
Teratogenesis and causes kernicterus – avoid in pregnant/lactating women
Hepatitis – rare
Causes rise in creatinine but does not represent renal failure
246
Function of HA and NA in Influenza
HA – binds virus to host cells
| NA – release of progeny cells
247
Which receptor does EBV enter from
Host cells = B-cells; enters B-cells via CD21 receptor
248
Cancers associated with EBV
nasopharyngeal carcinomas, Burkitt’s lymphoma, Hodgkin’s disease and B-cell lymphoma
249
CMV - Renal Bx finding
cytoplasmic inclusion bodies
250
BK Virus - Renal Bx finding
intranuclear inclusion bodies
251
BK virus staining
Positive SV40 staining
252
Rickettsia
Triad: Fever, rash, Hx of tick bite
- Non specific features
- Palm/sole rash is characteristic (late disease)
RF: Kids, Exposure to dogs, woods, seasonal
Tx: Doxy/Azithro
253
Ross river fever
From mosquitos
Features:
-Polyarthralgia - acute and symmetric, fever, rash,
254
LEptospirosis
Weils’ disease – jaundice, acute kidney injury, hypotension and haemorrhage (commonly lungs but can also affect GIT, pericardium brain)
255
Tx of schisto
Praziquantel
256
Chancroid
painful pustules that bursts and forms deep ulcers with erythematous bases; LND
haemophilus ducreyi
257
Lymphogranuloma venereum
chlamydia trachomatis
Painless ulcerations
Lymph involvement large tender LN, anorectal masses/proctitis/tenesmus
Late – fibrosis and strictures
Tx: doxy/azithro
258
Gonorrhoea Tx
Ceftriaxone + azithro/doxy
259
Chlamydia
azithro/doxy
260
Tx of cryptococcus
amphotericin B deoxyscholate PLUS flucytosine for at least 2 weeks
Then consolidation with fluconazole
261
Colistin SE
```
Nephrotoxicity
Urine infection
Neurotoxicity
Hypersensitivity
Bronchospasm when aerolised; give ventolin first
```
262
50s Protein synthesis inhibitors
Clindamycin
| Erythromycin
263
30s Protein synthesis inhibitors
Aminoglycosides
| Tetracyclines
264
Both 30s and 50s protein synthesis inhibitors
Linezolid
265
Blocks folic acid synthesis in the cytoplasm
Sulfonamides
| Trimethoprim
266
Cell wall inhibitors
```
Penicillins
Cephalosporins
Carbapenems
Vancomycin
Fosfomycin
Isoniasid
```
267
Attacks cell membranes and causes loss of selective permability
Daptomycin
| Polymyxins
268
Inhibits RNA polymerase
Rifampin
269
Inhibit replication and transcription. Inhibit gyrase (unwinding enzyme)
Quinolones
