ID Flashcards
(171 cards)
1
Q
Zika
A
humans and non-primates are reservoirs
Transmission:
- intrauterine, intrapartum, sex, blood transfusion, lab exposure
Sex: usually male to female.
prolonged viraemia in pregnant women; no evidence of increased susceptibility or severity in pregnant women
Safe sex for 3 months (male) and 2 months (female) after at risk travel
Incubation: 3-14 days (med 5 days)
Sx:
Rash (97%) for 6 days
Pruritis, HA, arthralgia, myalgia, nonpurulent conjunctivitis
fever in 50%
**
Complications:**
- congenital zika syndrome (fetal sequelae worse if infected in first trimester) can occur with both symptomatic and asymptomatic infection
>microcephaly with partial collapsed skull
>thin cerebral cortices with calcifications
>macular scarring and focal retinal mottling
>congenital contracture
>marked early hypertonia and extrapyramidal sx
diagnosis
- nucleic amplification tests (<7days of illness)
any bodily fluid - urine viraemia last longer than blood
- serology after 7 days (may be positive for years) - false negative is possible. can X react with other flaviviruses and vaccines
Symptomatic and pregnant: serum and urine for Zika virus PCR, dengue seum PCR and Dengue IgM
- USS after 4 weeks of infection, then regularly
Zika Virus exposure may breastfeed as transmission through breast milk has not been described although the virus is detectable in breast milk.
2
Q
Do you add CS for TB meningitis?
A
YES, lower mortality rate
3
Q
HIV and TB
A
Management of treatment-naïve HIV-infected patients with TB is especially challenging in areas with high rates of coinfection. Initiation of antiretroviral therapy (ART) may be complicated by the immune reconstitution inflammatory syndrome (IRIS), which can manifest as reactivation of latent TB, progression of active TB disease, or clinical deterioration in patients previously improving on antituberculous therapy.
For ART-naïve HIV-infected patients with CNS TB, initiation of ART should be delayed for the first eight weeks of antituberculous therapy, regardless of CD4 count. Treat TB first, then start ART after 8 weeks
All HIV-infected patients with TB be treated with ART. The optimal timing depends on the patient’s immune status:
For HIV-infected patients with pulmonary TB and CD4 cell count** <50 cells/microL,** initiation of ART within two weeks after starting TB treatment
For HIV-infected patients with pulmonary TB and CD4 count ≥50 cells/microL, initiation of ART within eight weeks after starting TB treatment
For HIV-infected patients with TB involving the central nervous system (CNS), ART should be delayed for the first eight weeks of antituberculous therapy, regardless of CD4 count.
For HIV-infected patients with baseline CD4 cell count <100 cells/microL on antituberculous therapy and initiating ART within 30 days of starting antituberculous therapy, prophylactic administration of prednisone during the first four weeks following initiation of AR may be considered to reduce the risk of IRIS
4
Q
Syphilis
What are non-treponemal tests?
A
RPR and VDRL
Non-specific for syphilis: can be false positive in: pregnancy, SLE, APLS, TB, leprosy, malaria, HIV
**It become negative after treatment **
5
Q
Syphilis
What are the treponemal specific tests?
A
realitative only
TP-EIA, TPHA
6
Q
Syphilis
What do the test results mean?
A
- Positive non-treponemal test + positive treponemal test —> consistent with active syphilis infection
- Positive non-treponemal test + negative treponemal test–> consistent with a false-positive syphilis result e.g. due to pregnancy or SLE (see list above)
- Negative non-treponemal test + positive treponemal test : consistent with successfully treated syphilis
7
Q
ESCHAPPM
A
E: Enterobacter spp.
S: Serratia spp.
C: Citrobacter freundii
H: Hafnia spp.
A: Aeromonas spp.
P: Proteus spp. (P. vulgaris)
P: Providencia spp.
M: Morganella morganii
Inducible beta lactamases
8
Q
Which ceph has poor cover against gram positive organisms (including strep pneumoniae)?
A
Ceftazidime
9
Q
Why ganciclovir in CMV?
A
Ganciclovir was the first antiviral agent approved for the treatment of cytomegalovirus (CMV) infection. It is widely used for the treatment of CMV infections among patients with impaired cell-mediated immunity, particularly persons with poorly controlled and advanced HIV/AIDS, and recipients of solid organ and bone marrow transplantation, who are at high risk for invasive CMV disease.
The drug is converted intracellularly to ganciclovir 5’-monophosphate by a viral kinase, which is encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells.
Unlike acyclovir, ganciclovir has poor bioavailability (6%) and is therefore given intravenously
10
Q
What are the main side effects of colistin?
A
Neuro and nephro toxicity
bacteriocidal abx
causes disruption to outer cell mb
11
Q
Indications for surgery for native valve endocarditis?
A
- valve dysfunction causing HF
- Paravalvular extension - abscess, fistula, heart block
- difficult to treat pathogen
- Persistent infection >7days
- Reccurent emboli and elarging vegetations
- mobile vegetation >10mmon the MV or AV with one or more other relative indications
12
Q
Can PJP be cultured?
A
no, but the organism needs to be visualised - this can be done with immunofluorescence
12
Q
Can PJP be cultured?
A
no, but the organism needs to be visualised - this can be done with immunofluorescence
13
Q
Why is valacyclovir better than acyclovir?
A
- faster resolution of acute neuritis
- lower rates of post hepatic neuralgia
14
Q
Which antifungal or antibacterial medication causes blue-green visual aura?
A
Voriconazole
15
Q
Side effects of voriconazole?
A
- visual changes
- hallucinations
- prolonged QTc
- neuropathy
- CNS alterations - memory, concentration
- alopecia
- photosensitivity rash (linked to SqCC)
16
Q
Valacyclovir and acyclovir
A
- Valacyclovir acts as a prodrug for acyclovir
0 Are phosphorylated by virally-encoded thymidine kinase and subsequently by cellular enzymes, yielding acyclovir triphosphate - Acyclovir triphosphate competitively inhibits viral DNA polymerase
17
Q
Penicillin allergy and other beta lactams
A
There is approximately two percent cross reactivity between penicillin and cephalosporins. There is approximately 1% cross reactivity between penicillin and carbapenem. There is no cross reactivity between penicillin and monobactams therefore aztreonam is the most appropriate response.
18
Q
A
The most frequent causes of brain abscess are Streptococcus and Staphylococcus spp; among these species, viridans streptococci and Staphylococcus aureus are the most common
Paranasal sinuses – Streptococcus spp (especially S. milleri), Haemophilus spp, Bacteroides spp, Fusobacterium spp
●Odontogenic sources – Streptococcus spp, Bacteroides spp, Prevotella spp, Fusobacterium spp, Haemophilus spp
●Otogenic sources – Enterobacteriaceae, Streptococcus spp, Pseudomonas aeruginosa, Bacteroides spp
●Lungs – Streptococcus spp, Fusobacterium spp, Actinomyces spp
●Urinary tract – Pseudomonas aeruginosa, Enterobacter spp
●Penetrating head trauma – Staphylococcus aureus, Enterobacter spp, Clostridium spp
●Neurosurgical procedures – Staphylococcus spp, Streptococcus spp, Pseudomonas aeruginosa, Enterobacter spp
●Endocarditis – Viridans streptococci, S. aureus
●Congenital cardiac malformations (especially right-to-left shunts) – Streptococcus spp
19
Q
Paradoxical reaction to anti-TB medications
A
- enlargement of LN size
- occurs in about 20% of pts
- usually occurs between 3 weeks to 4 months
- Culture negative
- ## Male gender is predictive
20
Q
MOA of antifungals in general
A
Azole: inhibits Ianosterol 14-a demethylase (CYP450), which converts Ianosterol to ergosterol –> damage to cell mb –> death
Amphotericin: binds to ergosterol and forms pores
Echinocandins: inhibits the enzyme that generates beta glucans
Flucytosine: inhibits DNA synthesis
21
Q
Donovan bodies
A
Granuloma inguinale
22
Q
Mechanism of acyclovir resistance?
A
●Reduced or absent thymidine kinase
●Altered thymidine kinase activity resulting in decreased acyclovir phosphorylation
●Altered viral DNA polymerase with decreased affinity for acyclovir triphosphate
23
Q
Quantiferon gold sensitivity and specificity
A
Sensitivity ~80%
Specificity 98% in low TB pop with no RF
it may stay positive after successful TB treatment therefore cannot be used to assess outcome of treatment.
24
Antibiotics that have low association with developing C.diff colitis
Aminoglycosides, metronidazole, tetracyclines, teicoplanin, rifampicin and carbapenems
25
oral ACT (Artemether and lumefantrine combination therapy) absorption is determined by...
presence of rich, fatty food
26
EBV serology
- IgM and IgG antibodies directed against the Epstein-Barr viral capsid antigen (VCA) are usually present at the onset of clinical illness because of the long viral incubation period.
- IgM levels wane approximately three months later; thus, they are a reliable marker of acute infection in a clinically appropriate picture.
-IgG VCA antibodies persist for life and are a marker of EBV infection.
- IgG antibodies to EBV nuclear antigen (EBNA; a protein expressed only when the virus begins to establish latency) **begin to appear 6 to 12 weeks after the onset of symptoms **and persist throughout life. Their presence early in the course of an illness effectively excludes acute EBV infection.
27
Which CD4 count do you worry about toxo?
<100
28
What is the mechanism of fluoroquinolone resistance?
reduced permeability via cell wall
29
Drug reaction groups
Type A: can affect any individual and are predictable from the known pharmacologic properties of the drug
- make up 90% of all ADR
- i.e. diarrhoea from abx, gastritis from NSAID, aminoglycoside nephrotoxicity
Type B: Occue in susceptible patients, and cannot predict from pharmacologic properties of the drug
- less common 10%
- majority of hypersensitivity reactions mediated by immunological or inflammatory mechanism
- *In addition, there are reactions, referred to as idiosyncratic drug reactions and exaggerated sensitivity reactions, which present with symptoms that do not involve the immune system or inflammatory cells.
30
TB reactivation
High RF:
- AIDS
- HIV
- Transplantation
- Silicosis
- CKD on RRT
- Carcinoma of head/neck
- Recent TB <2yrs
- abnormal CXR with apical fibronodular changes
- TNF alpha inhibitors
Moderate RF:
- Treatment with GC
- DM
- Young age when infected <4y
31
What's different about ertapenam compared to other carbapenem
Narrower spectrum
Active against enterobacteriaceae, and anaerobes
Less active against: pseudomonas, acinetobacter, Gram positive (particularly enterococci and penicillin resistant pneumococci)
The major benefit of ertapenem over other carbapenems is that it has a long half-life and can be administered once daily.
32
Which antibiotics are NDM1 strain susceptible to?
Colistin, Tigecycline
33
Clostridium Difficile
- **Toxin B is essential for the virulence** of C. difficile and is more than 10 times more potent than toxin A on a molar basis for mediating colonic mucosal damage. Thus, strains lacking toxin A can be as virulent as strains with both toxins
- NAP1/BI/027 are hypervirulent strains
- **bezlotoxumab** (monoclonal antibody against toxin B) together with standard oral antibiotic therapy was associated with a lower rate of recurrent infection than oral antibiotic therapy alone
34
Botulism
-acute onset of bilateral cranial neuropathies associated with symmetric descending weakness
- Other key features include absence of fever, maintenance of alertness, and lack of sensory deficits other than blurred vision.
- The diagnosis of botulism is confirmed by identification of toxin in serum, stool, vomitus, or food sources or by isolation of C. botulinum from stool, wound specimens, or food sources. However, initial detection of toxin requires one to four days and anaerobic cultures often take up to six days for growth and identification of the organism. Because these confirmatory tests do not yield timely results, the decision to administer antitoxin should be based on the presumptive clinical diagnosis of botulism and not be delayed while awaiting results of confirmatory diagnostic studies. (
35
Which medications are not used in MDR-TB treatmetn
Rifampicin
Isoniazid
Rifabutin
Thiacetazone
Augmentin
Macrolides
36
What si the hallmark feature of diffuse scleroderma?
Tendon friction rubs
37
When to use steroids with PJP tx
CS within 72hr of anti PJP treatement helps to prevent respiratory failure and death in AIDS patients.
All patients with A-a gradient >45 or PaO2 <70 should receive corticosteroids when antimicrobial therapy is initiated.
38
Treatment for MAC
Clarithromycin or Azithromycin + Ethambutol +/- Rifabutin or Rifampicin
## Footnote
Penicillin is not effective
39
Tropic diseases with incubation <10d
Dengue
Yellow fever
Zika
Chikungunya
Infuenca
Enteric infections
Rickettsial infection
40
Tropical disease with incubation period 10-21
Malaria
Thyphoid
Leptospirosis
Brucellosis
41
Incubation period >21days in tropical disease
Hep A/B/E
Schistosomiasis
TB
Leishmaniasis
**vivax malaria**
Meliodosis
Trypanomiasis
42
Tropical diseases with fever and rash
Dengue, Chikungunya, Rickesttsial infection, enteric fever, measles, acute HIV infection
43
# Tropical Diseases
Fever and abdominal pain
Enteric fever, Amboebic liver absces
44
# Tropical Diseases
Fever lasting >2 weeks
Malaria, enteric fever, EBV, CMV, toxo, acute HIV, acute schistosomiasis, brucellosis, TB, Q fever, visceral leishmaniasis
45
# Tropical Diseases
Fever ONSET >6weeks of travel
**Plasmodium vivax or ovale **
Acute Hep B,C, E
TB
Amoebic liver abscess
46
P. falciparum tx:
Central America: Chloroquine
Otherwise: Artemether-Lumafantire or Atovaquone-proguanil
47
P. Vivax or ovale tx
PNG/Indonesia: Chloroquine resistant, thus tx with Artemether-Lumafantrine, them **primaquine**
Otherise:
Chloroquine, then Primaquine
## Footnote
For **Primaquine** need to screen for G6PD activity
Tafenoquine is the new kid on the block - single dose, but need more G6PD activity
48
P. Knowlesi
Forest area in SE asia
Need PCR
REsponds to chloroquine
49
Severe malaria
High parasitaemia >10%
End organ dysfunction
Tx. IV artesunate
50
Malaria inx
Sporozoites to Liver
Thick film: screening
Thin: density and specification
51
Which species causing malaria has cyclic fever every 48h?
Plasmodium vivax/ovale
52
Which species causing malaria is associated with nephrotic syndrome?
Plasmodium malariae: cyclical fever every 72 hours
Plasmodium malariae: is associated with nephrotic syndrome.
53
Can you use ACT in pregnancy?
No
54
Leishmaniasis
- intracellular protozoa Leishmania
**- bites of sandflies**
- Different forms: Cutaneous, mucocutaneous leishmaniasis and visceral forms are seen
**Cutaneous**:
- caused by tropica or mexicana
- crusted lesion at the site of bite +/- underlying ulcer
- if caught in South/Central america - it needs treatment due to risk of transformation to mucocutaneous
**Mucocutaneous:**
- braziliensis
- skin lesions spread to mucosa
**Visceral:**
-mostly caused by** Leishmania donovani**
- occurs in the Mediterranean, Asia, South America, Africa
Sx:
Fever, sweats, rigors
Grey skin (Kala-azar)
Pancytopenia with hepatosplenomegaly
**Need BM for dx**
55
Trypanosomiasis
- African trypanosomiasis (sleeping sickness)
- American trypanosomiasis (**Chagas' disease)**.
56
# Trypanosomiasis
African trypanosomiasis, or sleeping sickness
- Trypanosoma gambiense in West Africa - Trypanosoma rhodesiense in East Africa.
Both types are spread by the** tsetse fly. **
Trypanosoma rhodesiense tends to follow a more acute course.
**Clinical features include:**
- Trypanosoma **chancre **- **painless** subcutaneous nodule at site of infection
-** intermittent fever**
- enlargement of posterior cervical lymph nodes
- later: central nervous system involvement e.g. somnolence, headaches, mood changes, meningoencephalitis
**Treatment:**
- IV pentamidine or suramin (early)
- later disease or central nervous system involvement: **IV melarsoprol**
57
# Trypanosomiasis
American trypanosomiasis, or Chagas' disease,
Trypanosoma cruzi
- The vast majority of patients (95%) are asymptomatic in the acute phase although a **chagoma **(an erythematous nodule at site of infection) and **periorbital oedema** are sometimes seen.
- Chronic Chagas disease affects **heart and GIT**
- CM or arrthythmias
**- Megaoesophagus/Megacolon**
**Treatment:**
- benznidazole or nifurtimox
58
****Interesting facts about rabies
RNA rhabdovirus
**travels up the nerve axons towards the central nervous system in a retrograde fashion**
- hydrophobia: water-provoking muscle spasms
- hypersalivation
- Negri bodies: cytoplasmic inclusion bodies found in infected neurons
59
Lyme disease
- spirochete bacteria: Borrelia burgdorferi (North America), B. garinii, B. afzelii (Europe and Asia)
- spread by **ticks**
- needs tick attachment for >36h for infection
**Clinical Features:**
stage 1 (early localized stage: 7-14 d post-bite):
■ malaise, fatigue, headache, myalgias
■ **erythema migrans:** expanding, non-pruritic bulls-eye (target) lesions (red with clear centre) at site of tick bite
- **typically develops 1-4 weeks after the initial bite** but may present sooner
- usually painless, more than 5 cm in diameter and slowlly increases in size
- present in around 80% of patients
**Stage 2** (early disseminated stage: weeks post-infection):
■** CNS: **
aseptic meningitis
CN palsies (CN VII palsy)
peripheral neuritis
■ **cardiac**: heart block or myocarditis
Stage 3: persistent stage - months to years
*■ may not have preceding history of early-stage infection
■ MSK: chronic monoarticular or oligoarticular arthritis
■ acrodermatitis chronicum atrophicans (due to B. afzelii)
■ neurologic: encephalopathy, meningitis, neuropathy*
60
# LYme disease
Investigations
ELISA:
Ab to Borrelia burgdorferi
**Treatment:**
- Doxycycline or Amoxicillin or Cefuroxine
- -if you have erythema migrans, start Abx
**Ceftriaxone if stage 2-3**
61
Dengue
- Endemic regions: Asia, Central/South America, Africa, Northern Territory Australia
- Aedes aegypti
- endemic during rainy season
Clinical maifestations:
Dengue fever:
- **onset is sudden with high fever (**may be biphasic, lasts 2-7 days), severe headache (especially in the retro-orbital area), arthralgia, myalgia, anorexia, abdominal discomfort, and sometimes a **macular papular rash.**
- **Flushing**, a characteristic feature is commonly observed on the **face, neck, and chest.**
Dengue haemorrhagic fever:
- usually follows **second exposure/infection**
- 1. Acute onset of high fever for 2-7 days
2. Haemorrhagic menifestation
3. Platelet <100
4. Haemoconcentration (rising packed cell volume >20%) or other evidence of plasma leakage—for example, ascites, pleural effusions, low level of serum protein/albumin.
*plasma leakage is more specific/common
62
# Dengue
Investigations
* **Low platelet counts of <100 × 109/l.**
* Leucopenia early in the illness.
* Atypical lymphocytosis (>15%).
* Abnormal coagulation profile (prolonged activated partial thromboplastin time, prothrombin time, raised fibrinogen degradation products).
* **Reduced serum complement levels.**
Low albumin
abnormal LFTs
Acidosis
RT-PCR is more specific and sensitive and allows for detection of early infection
**Treatment is just supportive **
63
Schistosomiasis
## Footnote
parasitic **flatworm infection **
S. mansoni, S. japonicum and S. haematobium.
**Katayama fever**: acute infection
* fever
* urticaria/angioedema
* arthralgia/myalgia
* cough
* diarrhoea
* **eosinophilia**
Chronic infection:
- Eggs in cluster in bladder causing inflammation
- looks like calcification in bladder
-** Risk of Squamous cell bladder cancer **
Inx:
- schistosome antibodies in asymptomatic pt
- if symptomatic: gold standard is urine or stool microscopy
Tx:
single oral dose of **praziquantel**
64
Toxoplasmosis tx:
**Co trimoxazole** if not cerebral involvement
Cerebral toxoplasmosis accounts for around 50% of cerebral lesions in patients with HIV: CT: usually single or multiple ring-enhancing lesions, mass effect may be seen
management: **pyrimethamine plus sulphadiazine **for at least 6 weeks
65
Cryptosporidiosis
protozoal cause of diarrhoea
Cryptosporidium hominis and Cryptosporidium parvum
Sx: watery diarrhoea, abdominal cramps, fever (+/- sclerosing cholangitis, pancreatitis)
modified Ziehl-Neelsen stain (acid-fast stain) of the stool may reveal the characteristic r**ed cysts of Cryptosporidium**
Tx:
Nitazoxanide
Rifaximin
66
Strongyloides stercoralis
**threadworm** - human parasitic nematode worm
- present in soil and gain access to the body by penetrating the skin.
**- Features:**
- diarrhoea
- abdominal pain/bloating
- **papulovesicular lesions** where the skin has been penetrated by infective larvae e.g. soles of feet and buttocks
- **larva currens**: pruritic, linear, urticarial rash
- if the larvae migrate to the lungs a pneumonitis similar to Loeffler's syndrome may be triggered
Eosinophilia
Treatment:
**ivermectin and albendazole** are used
67
Amoebiasis
Entamoeba histolytica
spread by faecal oral route
causes liver and colonic abscess
Long incubation
Dysentery - stool micro shows trophozoites - tx with **metronidazole **
Liver abscess:
most common in liver (hematologic spread); presents with right upper quadrant pain, weight loss, fever, hepatomegaly
for invasive disease or cyst elimination: follow with **iodoquinol or paromomycin**
68
Thyphoid
Enteric Fever
Salmonella enterica - Serotype: typhi, paratyphi A, B, C
**Humans are the only reservoir**
- direct and contaminated food/water
Incubation:
5-21 days
Sx:
Week1: Fever >1/52, relative bradycardia
Week 2: Abdominal pain, **rose spot**
Week 3: Septic shock, hepatosplenomegaly, perforation
BM has high sensitivity
Widal test: positive test may indicate past exposure
**Treatment:**
1. Ciprofloxacin or Ceftriaxone or Azithromycin
2. If from Pakistan: Carbapenam
3. Dex in severe infection
Long term damage to biliary tract sx in 1-6%, more common in women
69
NS1 - in dengue
- sensitive marker in first 5 days
- toxic properties that disrupts the endothelial glycocalyx --> vascular permeabilty --> plasma leakage --> dengue shock sx
70
What is the main characteristic symptom of Chikungunya
Severe arthralgia
Symmetrical joint pain in >90%
Itchy rash
Incubation 3-7
71
Candida
Most common species: Candida albicans
OthersL
parapsilosis, glabrata (glabrata is rising)
tropicalis, krusei
72
RF for candida infections
Cancers: Solid >haem>post-transplant
GI conditions
Chronic CVD
DM
Pancreatitis and HIV (rare)
Antibiotics - most common
IDVC
Major surgery
TPN feeding
73
RF for non albicans candidaemia
widespread fluconazole use
74
Risks for mortality with candida infection
Age >65
ICU admission
Chronic organ dysfunction
Surgery within 30 days
Haem malignancy
source of candidaemia
antibiotic therapy >10d
75
# Candademia
Investigations/Dx
- Blood culture
- beta-D-glucan, whole blood PCR
76
Which candida organism is contributing to increasing resistance?
C. glabrata
77
Antifungal MOA
Ergosterol synthesis: (inhibit C-14a demethylase)
- azoles
- terbinafine
- naftifine
affecting mb function:
- Amphotericin B
Cell wall synthesis:
- caspofungin
Nucleic acid synthesis:
- 5-fluorocystosine
78
Voriconazole
Addition of methyl group to fluconazole backbone
broader cover (**including fluconazole resistant Candida)**
ADR:
-Visual SE, photosensitivity, LFTs
Need therapeutic monitoring
79
Amphotericin
Treatment for resistant candidaemia
Binds to sterol and increase mb permeability and lead to pore formation
- conventional: **nephrotoxic**
**Liposomal AmB:**
Bind preferentially to fungal wall
less nephrotoxic and infusion reaction
**better CSF penetration**
80
Echinocandins- caspofungin
Inhibit synthesis of beta-1-3-D-glucan (**inhibit fungal cell wall synthesis**)
97% protein bound
metabolised by hydrolysis and N-acetylation
No renal adjust, but adjust for severe liver disease
**Interactions:**
- cyclosporin A, Tacrolimus, ART, phenytoin, Carbamazepine, Rifampicin
Broad spectrum, **but it doesn't cover for C. parapsilosis**
81
Candida auris
Emerging drug resistant yeast
high mortality
Antifungal resistance is common including Echinocandins and AmB
Tx: first line is **echinocandins**
82
Bacteriocidal antibiotics
**V**ery **F**inely **P**roficient **A** t **CC**ell **M**ur**D**er
Vancomycin
Fluoroquinolones
Penicillin
Aminoglycosides
Cephalosporins
Carbapenams
Metronidazole
Daptomycn
83
Bacteriostatic
**ESCT**a **T**i**C**
Erythromycin and other macrolides
Clindamycin
Sulfamethoxazole
Trimethoprim
Tetracyclin
Chloramphenicol
84
Antibiotics site of action
Penicillin
Cephalosporin
Carbapenam
Glycopeptide
Cell wall
85
Antibiotics site of action
- Rifampicin
- Fluroquinolones
- Nitrofurantoin
- Isoniazide and ethambutol
Rifampicin: RNA polymerase
Fluoro: DNA gyrase
Nitrofurantoin: protein synthesis
Isoniazid and ethambutol: mycolic acid pathway
86
Antibiotics site of action:
Macrolides
Aminoglycosides
Tetracycline
TMP/SMX
Dapsone
Metronidazole
- 50s ribosome
- 30s ribosome
- 30s ribosome
- Folic acid pathway
- Folic acid pathway
- Toxic metabolites
87
What is the common cause of C. difficile diarrhoea
clindamycin
88
Which antibiotics is known to prolong QTc?
Macrolide
IT's also a CYP3A4 inhibitor
89
# Antibiotics
Aminoglycosides
30S ribsome inhibitor
- good for circulating organisms
- poor tissue, bone, lung, abscess, CSF penetration
ADR: nephrotoxicity (ATN), Ototoxocity
90
B-lactam are good for abscesses?
FALSE
91
Drugs with good tissue penetration
Tetracycline
Macrolides
Quinolones
Clindamycin
92
Antibiotics that do not need renal adjustment
MAcrolides
Fusidic acid
Clindamycin
93
Tell me about tetracycline metabolism?
Concentrated in the liver, excreted bia bile and reabsorbed in intestine, eliminated in urine
Avoid in liver failure
94
Antibiotics and liver failure
Penicillin safe - but can cause cholestatic jaundice
Aminoglycoside: safe
Glycopeptide: safe
Tetracycline: AVOID
Macrolide: may worsen liver dysfunction
**Co-trimoxazole - aVOID** - *significantly metabolised by the liver *
95
Which generation of cephalosporins have antipseudomonal property
Ceftazidime (3 gen), Cefepime (4th gen)
96
Cephalosporin with MRSA cover?
Ceftaroline (MRSA cover)
97
Betalactam: MOA
Mimic building block of bacterial cell wall - bind to PBP --> inhibit cell wall synthesis --> death
98
What is the mechanism of betalactam cross reactivity?
R1 side chain
99
Cefazolin doesn't share side chains with penicillin or other cephalosporins?
TRUE
100
What is the mechanism of B-lactam resistance?
modification of PBP
*mec*A gene encodes a new PBP 2a
## Footnote
**Intrinsic resistance to enterococcal (as doesn't bind to PBP)**
101
ESBL
carries on plasmid, thus can pass to other organisms
- can use **carbapenam **
102
AmpC
Broad spectrum cephalosporinase
Intrinsic to ESCAAPPMS
**use cefepime or carbapenam**
103
Overcoming Betalactamase production
1. use a stable beta lactam, i.e. flucloxacillin (*penicillinase staph*) or Carbapenam stable vs ESBL/AmpC
2. combine with beta lactamase inhibitor (not reliable tho)
3. Use different class
- Cotrim, cipro, gent for ESBL
- Colistin, tigecycline, fosfomycin for carbapenamases
104
Which enterococcus is susceptible to penicillin?
E. faecalis is amoxicillin susceptible
Enterococci are intrinsicly resistant to cephalosporins
105
Why do you add amoxicillin to cef for meningitis in elderly?
to cover for listeria
which is a G+ve rod
106
Line infections:
When to remove:
- if pt really unwell
- tunnel or entry site infection
- persistently postive BC despite tx
- Organisms:
> S. aureus, Candida, pseudomonas, other GN non-fermenters
107
Glycopeptides
- BIG
- can't cross the outer mb of gram negatives, so only for GRAM POSITIVE
- MUST BE IV
- Red man syndrome with vancomycin, not teicoplanin
- inhibits cell wall synthesis
108
Glycopeptide resistance
D-ala, D-ala to D-ala, D-lac
Van A/B
**prevents binding of antibiotic to cell wall constituents**
Alt antibiotics:
- Linezolid
- Daptomycin
- Tigecycline
109
IS clindamycin a macrolide?
NOOOOOO
IT's a lincosamide
110
Macrolids
Active against organisms that don't have a cell wall as well
GI SE: Erythro>Clarithro >azithro
Good tissue penetration and intracellular (esp Azithromycin for **legionella, typhoid**
It also has antiinflammatory/immunomodulatory effects
111
Clindamycin
Lincosamide
50s ribosome
Inhibits protein synthesis - good for toxic shock sx and nec fasciitis due to GAS (as it reduces toxin production)
associated with C.diff
**Very well obsorbed orally**
Excellent tissue penetration (good for skin and soft tissue)
**Good Anaerobic activity **
112
Tetracyclin
Ribosome 30s
active against organism without cell wall e.g. mycoplasma
Active against intracellular organism: ie Rickettsia
Gram POSITIVE and gram NEGATIVE activity
useful against MRSA
ADR:
Discolouration of bone and teeth
Mucosal irritation - take with food
Photosensitivity
**Resistance is via EFFLUX mechanism**
## Footnote
NOT for young or PREGNANT
113
Rifampicin
Inhibit RNA synthesis
Excellent tissue penetration
Antituberculous activity
**antibiofilm**
*useful in infections onvolving prosthetic materials*
**Red/orange discolouration of bodily fluids**
Can easily develop resistance due to change in RNA polymerase. NEVER use alone
STRONG CYP450 **inducer**
114
Aminoglycosides
Gentamicin, Tobramycin, amikacin
Doesn't cross BBB
poor tissue penetration
not good for abscesses
GOOD for bacteraemia
Not absorbed orally, so IV only
115
What;s the treatment for stenotrophomonas maltophilia?
Co-trimoxazole
116
Folate pathway inhibitos
TMP and SMX
They inhibit 2 different part of the pathway, thus reduces resistance when combined
TMP is teratogenic in 1st trimester
Rare, but can cause myelosuppression
Co-trim:
- PJP, and Toxo tx
- Useful for MRSA, ESBL/AmpCs
- Active against Stenotrophomonas, Burkholderia, pneumocystis
- Associated with low risk of **SJS**
117
Quinolones
Inhibit DNA gyrase
Very useful for resistant **gram negative**
IT is the only ORAL agent against pseudomonas
Moxifloxacin (resp quinolone) is useful for penicillin resistant pneumococci + TB
Good ORAL absorption
Good tissue penetration
Good for OP pyelo
Good ANTIBIOFILM
**Mutation in DNA gyrase can cause resistance**
Cipro is associatd with **hypervirulent strain of C.diff (ribotype 027)**
ADR:
- tendonitis
- Aneurysm rupture
- Cognitive impairment
- hypoglycaemic coma
- Worsening MG
- **irreversible** peripheral neuropathy
118
Pharmacodynamics of antibiotics to know
Aminoglycosides: Cmax>MIC
B-lactam: time >MIC
Vancomycin: AUC>MIC
119
Linezolid
Oxazolidinone inhibits protein synthesis
GRAM POSITIVES only
use in VRE, MRSA
ADR: myelosuppression
Peripheral and optic neuropathy
Serotonin syndrome when used with other MAOi or Tramadol
Lactic acidosis
120
Daptomycin
Cyc Lipopeptide
IV only
GRAM POSITIVE ONLY
VRE and MRSA
**inactivated by surfactant**
ADR: rhambomyolysis - check CK
121
Tigecycline
Glycylcycline
IV only
Active against **MRSA,**
and many of the multi drug drug resistant GRAM NEGATIVES (ine. NDM
Remember: not good for bacteraemia
122
Fidaxomicin
Treatment of C. diff
NOT ABSORBED
reduced risk of relapse cf. vanc
123
Colistin
Binds to LPS and lipids in the bacterial cell mb
Active against many GNB and new resistant organism
RENAL toxicity
can develop resistance via mcr-1 gene --> causing changes to outer mb
124
Fosfomycin
Inhibits MurA enzymes
used for resistant UTI (AmpC, ESBL)
SE: GI
125
Panton-Valentine- Leucocidin (PVD)
pore forming necrotising endotoxin
related to MRSA
126
What do you use for MRSA (non-multiresistant)?
Cotrim
Clinda
Erythro
Doxy
Rifampicin (don't use alone)
Fusidic Acid (dont use alone - not used in NZ due to resistance)
Gent
127
Severe MRSA
Glycopeptides
- remember higher the MIC, higher the treatment failure
Linezolid (100% absorbed) - static
- binds to both 30s and 50s ribosomal subunits
- suppress toxin production
- good penetration: bone, lung, CNS
- **New: Tedizolid = better version**
DAPTOMYCIN:
- bacteriocidal
Tigecycline:
- eliminated in biliary tract, less useful in UTI
- Active against Acinetobacter and stenotrophomonas
- NOT active against pseudomonas, proteus, providencia
- high Vd, thus not good for bacteraemia
128
Ceftaroline: 5th gen
like 3rd gen, but has MRSA cover
renally cleared
active against Gram+Ve bacteria (including coagulase negative)
Active against VRE.faecalis (NOT Faecium)
Limited activity against G-ve
NOT ACTIVE against: pseudomonas, or AmpC or ESBL
**Ceftobiprole:** 5th gen, like above, but **with pseudomonas cover**
129
Enterococci
Gram positive cocci
Group D Strep formally
Inherently resistant to ceph
E. faecalis:
-susceptible to penicillin
- More virulent
E. Faecium:
- less virulent
- resistant to penicillin
## Footnote
Enterobacter: GN rod
130
Van A and Van B
D-ala-D-ala to D-ala-D-lac
A: is resistent to both Vanc and TEicoplanin
B: is only R to vanc
A/B are transferable
131
Penicillin resistance can be overcome if penicillin concentration at the target site is above the MIC for the organism for **40-50%** of the dosing interval
TRUE
## Footnote
CNS penicillin concentration is much lower than plasma 0.5-5%
132
Macrolide resistance
mefA: efflux pump - low level of R
ermB gene - alteration of binding site, high level of resistance
**MAcrolide resistance CANNOT be overcome by higher doses**
133
What is most common mode of R in GN againt beta lactams?
beta lactamases
134
# Beta lactamases
AmpC beta lactamases
ESCHAPPM:
**Enterobacter
Serratia marcescens
Citrobactor fruendii** *C. koseri doesn't have AmpC*
Hafnia alvei
Acinetobacter and aeromonas
Proteus vulgaris *P. mirabilis doesn't have AmpC*
Providencia
Morganella morganii
Inducible resistance to cephalosporins
(except **Cefepime**)
Tx options:
Carbapenems and cefepime, whilst awaiting susceptibility
## Footnote
AmpC is on plasmid
- so they can swap with other bacteria
135
ESBL
- all penicillin, ceph (including cefepime) and aztreozam (monobactam)
- most commonly found on E.coli, and Klebsiella
- on PLASMID = transferrable
may also carry other non-betalactam resistance
Tx:
**Carbapenam** are the first choice
136
CRE
1. KPC: Klebseilla pneumoniae carbapenamases : Europe, South America, China, SE Asia, some US
2. New Delhi Metallo-beta-lactamase proteinase (NDM) - India
3. OXA-48: Oxacillin-type beta lactamase-48 (Turkey)
4. VIM - Verona-integron-encoded metallo-beta lactamase- australia
5. IMP
**Treatment options:**
1. Colistin or PolymixinB
2. High dose tigecycline (not useful for bacteraemia)
3. Aminoglycoside (Gent, Tobramycin, Amikacin)
4. Double carbapenam tx ???
137
Avibactam
Second gen beta lactamase inhibitor
It binds to the beta lactamase enzyme and inactivates it **(reversible cyclisation)**
It can inhibit:
Class A: ESBL, KPC
Class C: AmpC
Class D: Oxa-48
NOT:
NDM
VIM
IMP
**Ceftazadime-avibactam is good for KPC**
138
HIV basics
HIV uses gp120 and gp41 to attach to CD4, then to CCR5 or CXCR4
CD4+ are the only cells that can be infected; this includes Th, monocytes, macrophages, dendritic cells, microglial cells
Strains that can bind either CXCR4 or CCR5 replicate rapidly and deplete CD4 cells faster
if you don't have CCR5, then you can't be infected (del mutation found on 1% of europeans)
~3-4 weeks after the infection, HIV viral load will be 10^6/mL, then CD8 cells starte killing the infected cells, reducing it to 10^4. B-cells produce Ab against HIV infected cells.
Killing of large number of CD4 infected cells --> glandualr fever like seroconversion illness
**antibodies will be falsely negative for 3-4 weeks**
**CTL only kill CD4 cells that are producing HIV, not the dormant ones. ~99.9% of infected CD4 cells are not producing HIV**
HLAB*57.01 binds a HIV core protein peptide strongly and activates CTL. Slower progression of disease
139
HIV markers detection with time
HIV NAD detection 11 days
p24 from 16 days
Antibody 3-4 weeks
140
HIV management
## Footnote
All HIV medications are tolerated in pregnancy
Undetectable = no transmission
Start treatment at all CD4 counts
Naive patients:
- INSTI + 2 x NRTI
- INSTI + 1 x NRTI (except for:
>HIV RNA >500, 000
>HBV coinfection
>if ART to be started before resistance profile is known
- other option (single tablet): Efavirenz + Emtricitabine/tenofovir)
When to start if they have:
1. TB:
CD4 >50, then 8-12 weeks after starting antiTB medications
if CD4<50, the 2 weeks after antiTB medications
if TB meningitis, then delay until onset of Anti-TB txmt
## Footnote
Intergrase inhibitor (INSTI): "gravir"
PIs: "avir"
141
# HIV
NRTI
NRTI:
- inhibits viral reverse transcriptase
- FTC: Emtricitabine (low barrier to resistance)
- 3TC: Lamivudine (low barrier to resistance)
- ABC: Abacavir *hypersensitivity with HLA B57*01, CVD*
- AZT: Zidovudine *lipodystropgy, metabolic toxicity, GI*
- TDF -nephrotoxicity (prox. tubular cells), reduced BMD, monitor creat, phosphate, mitochondrial toxicity
- TAF (better, less renal toxicity)
142
# HIV
NNRTI
bind to RT (but not at deoxynucleiotide binding site)
- low barrier to resistance
- NVP - Nevirapine - **hypersensitivity, fatal hepatitis**
- EFV: Efavirenz **CNS - sedation/insomnia, vivid dreams. Rash (can continue, unlike Nvirapine. Increase LIPIDS and LFTs**
- Rilpiverine **Prolong QTc**
- Delaverdine , Rash HA
- Etravirine- rash, GI
- Doravirine
143
Protease inhibitor
| "avir"
Blocks viral maturation during and after budding of virions --> defective virus
High barrier to resistance
All have: GI SE,** Dyslipidaemia, IGT, lipodystrophy**
- Ritonavir: poorly tolerated *usually used to boost other PIs by inhibiting CYP3A4*
- Lopinavir - *more ritonavir SE*
- Atazanavir (elevated bilirubin, rarely renal stones)
- Darunavir (rash)
144
# HIV
INSTI
inhibit intergration of viral DNA into human DNA. Rapid reduction in viral load
- Dolutegravir (DTG) - high barrier to resistance
> HA, **Depression/anxiety**, possibly increase in neural tube defects
- Bictegravir (BIC):
> HA, GI, avoid dofetilide
- Raltegravir: low barrier, increase CK/rhabdo
- Elvitegravir
145
# HIV
Enfuvirtide
fusion inhibitor
146
Maraviroc
CCR5 antagonist
*remember the virus may switch to CXCR4
147
Key facts about Atripla
Efavirenz + Emtricitabine, tenofovir
CNS toxicity - suicidality
148
Dolutegravir + pregnany
pseudo increase in creatinine
ok in pregnancy
149
Cobicistat
no HIV activity
inhibits tubular secretion
150
# HIV
PrEP
- MSM/Trans:
**Not eligible for funded PrEP**
Insertive CLAI with any casual male partner (in last 3 months or expected in next 3 months)
Travelling to a high-HIV prevalence country and anticipates risk
**Heterosexual people:**
- High risk of HIV and eligible for funded PrEP
CLI with a regular HIV+ partner who is not on treatment and/or has a detectable viral load.
- Not eligible for funded PrEP; could consider self-funded PrEP
Receptive CLI with any casual MSM partner (in last 3 months or expected in next 3 months)
Travelling to a high-HIV prevalence country and anticipates risk
**Tx:**
1 pill daily of
**tenofovir/emtricitabine.**
Start 7 days before HIV risk.
Event driven:
tenofovir/emtricitabine:
* 2 pills at least 2h before sex
(up to 24h before sex)
* 1 pill 24h later
* 1 pill 48h after first dose
If repeated sexual activity, then
continue with 1 pill daily until
48h after last sexual contact
151
# HIV
PEP
- PEP within 72hrs is beneficial (animal studies only), greatest benefit <24h
- 28d course was better than shorter course
- non-occupational exposure to known HIV source, VL unknown: 3 drugs, *don't need it for oral sex
- Occupational: shorts and mucous mb exposure: if viral load is known to be undetectable 2 drugs, otherwise 3 drugs
2drugs:
- tenofovir + emtricitabine or lamivudine
3 drugs:
- NRTI as above + INSTI
152
# HIV
Risk of transmission
- Receptive anal sex with ejaculation (1/70), withdrawal (1/155)
- Shared needles (1/125), needle stick injury 1/440
- Uncircumcised - 1/160, circumcised 1/900
153
# HIV
Opportunistic infections
154
# HIV
Which OI can you get at any CD4 levels
TB
Oral thrush
pneumococcal pneumonia
VZV
Cervical ca
155
When can you have lives vacccines in HIV pt
CD4 count >200
156
# HIV
PJP
Primary prophylaxis when CD4 <200, until it's >200 for 3 months
Subacute presentation as fungus must synthesis it's own folic acid
It doesn't have ergosterol in it's wall, thus other antifungal is not effective
Sx:
SOB (91%)
Fever 66%
Cough 50% - non productive
Tachycardic, tachpnoeic, hypoxia but chest exam will sound normal
CT: widespread groundglass with **apical sparing**
Dx:
PCR of induced sputum 50-90% sensitive, 99% specific
BAL >90% diagnostic yield
Serum beta-D glucan - useful rule out
Tx:
Co-trimoxazole
if allergic:
- Pentamidine IV
- Dapsone or Atovaquone PO
- Clindamycin + PRimaquine
**STEROIDS if hypoxic PaO2<70 **
Prophylaxis:
- cotrim or neb pentamidine
OTher indication for PJP prophylaxis:
- Pred >20mg/day for >4 weeks
- ALL induction to end of maintenance
- Allo-HSCT
- Alemtuzumabm rituximab, ATG
- SOT
| Expect improvement in 4-8days
## Footnote
- Pentamidine: necrosis of islet cells
157
Whst is the best prognostic factor in PJP
PaO2 at diagnosis
Steroids improves mortality if given when PaO2<70
158
# HIV
Cryptococcocosis
- round yeast
- C. neoformans
- Usually occurs CD4 count <100, (50!!)
- usually disseminated when diagnosed
- Subacute meningitis (25% won't have meningeal sx)
- raised ICH: CN palsies, seizures but typically fever and confusion
Dx:
LP: **raised opening pressure**
Analysis can be normal, but may have raised protein and WCC, low glucose
CSF: Af 94%, Culture 100%, PCR 80%
**india ink and CRAG positive **
Managment:
1. LP to manage high pressure aim <25cm H2O
2. Induction (1 week):
Liposomal AmB + 5flucytosine
- 5FC is specifically converted to 5FU by fungal cystosine deaminase
3. Consolidation with fluconazole for 8weeks
ONLY START ART after 4-6 weeks once CSF is sterile, as it reduces the risk of IRIS --> mortality
IRIS in crptococcosis:
- fever, HA, high opening pressure, seizures, CN palsies, new MRI lesions wks/mo after ART
- tx: NSAIDs or prednisone
159
When does CMV and MAC occur in HIV pt
When CD 4 <50
160
# HIV
Toxoplasmosis
CD 4 <100 for brain abscess
px:
HA, fever, seizrues, AMS, focal deficits
Dx:
MUST HAVE **Toxo IgG + in serum**
PCR CSF for toxo
ring enhancing lesions on MRI (multiple)
Tx:
Co-trim
*used to use pyrimethamine + sulfadiazine or leucovorin, but out of favour now*
Should improve in 1-2wks
161
What are the predictors of IRIS?
high VL
low CD4
high pathogen burden
usually 6 weeks after starting ART
Tx: STEROIDS, NSAIDs
162
What is the risk of vertical transmission of HIV without treatment?
1/4
163
what do you do if VL >1000 or unknown at time of delivery?
give AZT (Zidovudine) and C-section
164
CMV retinitis
correlates with CD4 counts
not an indication for tx unless has organ disease
If immediate sight threatening lesion:
- ARV, IV ganciclovir
- Intravitreal ganc
Small peripheral:
ARV
Oral valganc
Improves within 2 weeks
165
Syphilis chancre
macule, papule, ulcer, then resolution over 3-6wks
plasma cell infiltrate
**typically painless single ulcer **
166
Latent TB treatment
9H=4R=3RH
~90% efficacy
Remember: H: 15% R worldwide, and severe hepatotoxicity
3mo H and rifapentin: higher completion rate, similar ADR, less hepatotoxic, increased rate of hypersensitivity
In HIV infecton: 1 month of daily H + rifapentin
167
Active TB treatment
- H +P: better for sterilising acitivity
- H+ R: prevention of R + early bacteriocidal activity
2 mo HZRE + 4 RH = 98% cure
168
What is the newer shortened regime for TB treatment?
Rifapentin + HZM or HM for 4 months
169
What are the ADRs for pyrazinamide?
Hepatitis, skin, polyarthralgia, gout
170
TB drugs and risk of hepatitis in order of probability
Z>H>R
If LFTS > 5 ULN or 3 x ULN with sx - stop or switch to Amikacin, Ethambutol, moxi
