Infections / antibiotics

Question 1

What are the species of candida that cause illness?

Answer 1

Candida:
- Albicans
- Tropicalis
- Parapsolosis
- Auris
- Glabrata
- Krusei

Question 2

What species of aspergillosis are associated with illness?

Answer 2

Aspergillosis:
- Fumigatus
- Flavus
- Niger
- Terreus

Question 3

What are the risk factors for invasive candidiasis?

Answer 3

1. Immunosuppression: Neutropenia, organ transplants, cancer, haem malignancy, HIV etc
2. Disruption to barriers: Indwelling catheters and prosthetic material, abdo surgery (bowel perf), acute pancreatitis, burns.
3. Broad spectrum antibiotics
4. Colonisation with candida spp.

Question 4

What are the risk factors for invasive aspergillosis?

Answer 4

1. Immunosuppression: Neutropenia, organ transplants, cancer, haem malignancy, high-dose steroids, HIV etc
2. Mod-to-severe COPD
3. Decompensated liver cirrhosis
4. Viral pneumonia (covid / flu)
5. Post ARDS

Question 5

What are the clinical manifestations of invasive candidiasis?

Answer 5

1. Catheter-associated bloodstream infection
2. CNS
3. Endophthalmitis
4. Endocarditis
5. Intra-abdominal infections

Question 6

What are the clinical manifestations of invasive aspergillosis?

Answer 6

1. Tracehobronchial aspergillosis (TBA)
2. Rhinosinusitis and CNS infections
3. Invasive pulmonary aspergillosis (IPA)

Question 7

How is proven invasive candidiasis diagnosed?

Answer 7

Candida isolated from a sterile site e.g. peripheral blood culture (not from a line) or from sterile sampling of other tissue

Question 8

How is probable invasive candidiasis diagnosed?

Answer 8

1. Risk factors present
2. Clinical or radiological features
3. Non-diagnostic mycology evidence e.g. B-D glucan

Question 9

What are the issues with using cultures to diagnose invasive candidiasis?

Answer 9

Slow to get a result and poor sensistivity

Question 10

In non-neutropenic patients, when should empirical antifungals be started?

Answer 10

Should be considered if multiple risk factors in patients with a persistent fever of unknown source whilst on broad spectrum antibiotics

Question 11

What is B-D glucan?

Answer 11

Detects fragments of fungal cell wall.
Low specificity but reasonable sensitivity.
Specificity is improved if 2 consecutive +ve results.
Helpful in the early cessation of empirical antifungals.

Question 12

What is the firstline treatment of invasive candida in critically unwell patients?

Answer 12

Echocandins - they are all fungicidal and borad spectrum. Resistance is rae but has been reported in C.glabrata, parapsilosis and auris.

Question 13

Where in the body do echinocandins not work effectively?

Answer 13

CNS
Eye
Urinary tract

Question 14

What is the firstline treatment of invasive candidiasis in patients who are not critically ill?

Answer 14

Fluconazole - unless they’re likely to have a spp resistant to it.
Resistance is intrinsic in C.krusei and increasing in glabrata, tropicalis and auris.

Question 15

How is invasive aspergillosis diagnosed?

Answer 15

Requires histopathological evidence combining +ve mycology plus tissue invasion.

Question 16

How is a diagnosis of probable invasive aspergillosis made?

Answer 16

1. Presence of risk factors
2. IPA requires CT chest confirming pulmonary infiltrates or cavity lesions. TBA requires a bronch confirming tracheobronchial ulveration, nodule, pseudomenbrane, plaque or eschar.
3. Mycology criteria:
   - aspergillosis +ve culture
   - +ve galactomannan from BAL (>1 optical density index)
   - +ve galactomannan >0.5 from serum

Question 17

What is first-line treatment for invasive aspergillosis?

Answer 17

Voriconazole / posaconazole or isuvaconazole.
Drug levels need monitoring.

Question 18

Where does staph aureus colonise?

Answer 18

Mucous membranes, skin and GIT.

Question 19

What factors increase the risk for nasal carriage of staph aureus?

Answer 19

Healthcare exposure, diabetes, dialysis, elicit drug use, HIV.

Question 20

What is the mortality a/w staph aureus bacteriaemia?

Answer 20

20-30%

Question 21

What is the likelihood of MRSA in North Europe vs USA?

Answer 21

< 5% Europe and ~ 50% USA.

Question 22

What key points need to be considered when managing a staph aureus bacteraemia?

Answer 22

1. Appropriate abx
2. ECHO
3. Assessment for metastatic phenomena and source control
4. Antibiotic duration
5. ID consultation

Question 23

What type of bacteria is S.aureus?

Answer 23

Gram +ve facultatively anaerobic coccus. Which means that it will use O2 to make ATP when it’s available but that it can also ferment.

Question 24

What is Panton-Valentin Leukocidin?

Answer 24

A toxin produced by S.aureus. that’s associated with granulocyte destruction. It can be associated with deep-seated infections in hosts with relatively high infl markers but relative leukopenia.

Question 25

What timing of growth on BCs suggests S.aureus line infection?

Answer 25

If the time difference to +ve BC is 2+ hours between a central BC and a peripheral BC then this is suggestive of a central-line associated blood stream infection.

Question 26

What are the 3 main ways that vancomycin resistance to S.aureus can develop?

Answer 26

1. Modifications to the bacteria cell wall 2. MIC creep (not a true resistance) 3. Acquisition of vanA plasmid - which alters the peptide target of glycopeptides

Question 27

Discuss appropriate abx therapy for S.aureus bacteriaemia

Answer 27

- Empiric monotherapy with vanc is a/w worse outcomes that with an anti-staph beta-lactam - When sensitivities are unknown a anti-staph B-lactam and anti-MRSA agent should be used followed by appropriate de-escalation - Anti-staph B-lactam or cefazolin are preferred and clinically superior in MSSA bacteraemia - Taz is a/w increased mortality - Vanc or daptomycin for MRSA is the preferred option. Linezolid is a/w increased mortality.

Question 28

What is the role of ECHO in S.aureus bacteraemia?

Answer 28

- It's use is supported by the European society of cardiology guidelines - 18% at least who have IE don't have peripheral stigmata - TOE has a higher sensitivity, both have similar specificity - TOE recommended in those with prosthetic heart valves or intra-cardiac devices - Those requiring a prolonged course of abx anyway don't need a TOE assuming TTW has ruled out surgical indications of native IE

Question 29

How do you assess for metastatic S.aureus infection

Answer 29

1. History - recent trauma, procedures, co-morbidities, foreign bodies, acute pain 2. ?Lines - they're the most common cause of hospital acquired S.aureus 3. ?Skin / soft tissue infections - most common cause of community acquired. 4. Exam - for soft tissue infection, IE stigmata, vertebral tenderness 5. Investigations - including MRI of spine if vertebral tenderness, even if subtle. May need to be repeated. Radiologcal signs can lag behind clinical signs by 10 days. PET-CT may be useful.

Question 30

How long should antibiotics be continued in S.aureus bacteraemia?

Answer 30

Uncomplicated - minimum 2 weeks from 1st negative BC Complicated - minimum 4 weeks. Deep-seated minimum 6 weeks.

Question 31

What defines an uncomplicated S.aureus bacteramiea?

Answer 31

1. S.aureus clearance within 48-72 hours following start of antibiotics. 2. Removable foci of infection 3. Absence of metastatic phenomona 4. No endovascular foreign material 5. No evidence of IE

Question 32

What are the indications for surgical management of IE?

Answer 32

1. Left-sided endocarditis (strong) 2. Endocarditis induced valve dysfunction resulting in heart failure (strong) 3. Endocarditis induced heart block, annular or aortic abscess, or destructive penetrative lesions (strong) 4. Persistent infection (persistent bacteremia or fever ≥ 5-7 days after initiation of anti-staphylococcal antibiotics) (strong) 5. Relapsing prosthetic valve endocarditis despite an appropriate antimicrobial course (mod) 6. Recurrent emboli and persistent vegetations despite appropriate antimicrobial therapy (mod) 7. Vegetations >10 mm in size with clinical evidence of embolic phenomena despite appropriate antimicrobial therapy (weak) 8. Right-sided endocarditis with symptomatic severe valve dysfunction AND evidence of persistent infection (weak)

Question 33

What PCT values did the ADAPT-Sepsis RCT use to discontinue antibiotics?

Answer 33

< 0.25 strongly suggested and a fall > 80% or PCT > 025 and < 0.5 was suggested stopping.

Question 34

What are the key features of botulism?

Answer 34

The 5Ds - diplopia - dysarthria -dysphagia - dyspnoea - descending paralysis Also afebrile, sore throat, autonomic dysfunctions, GI symptoms

Question 35

What are the causes of botulism?

Answer 35

- Clostridium botulinum - Gram +ve bacteria - Serotypes A,B+E cause human disease

Question 36

What are the main vectors of botulism?

Answer 36

1. Food - usually home preserved meat/fish/veg 2. Water - most common in Uk 3. Intestinal colonisation - infants 4. Deliberate - weapon 5. Iatrogenic - e.g. following botox 6. Wounds - IVDUs / skin popping

Question 37

What is the treatment of botulism?

Answer 37

1. Pen G for wound botulism 2. Antitoxin decreases severity of symptoms 3. FVC < 12ml/kg is a suggested indication for ventilation 4. Early micro/ID involvement 5. Wound debridement

Question 38

What is the differential diagnosis of botulism?

Answer 38

1. GBS 2. Polio 3. MG 4. Lambert-Eaton 5. Tick bite 6. Paralytic shellfish poisoning 7. Viral encephalitis

Question 39

What's the MOA of immunoglobulins in sepsis?

Answer 39

1. Oponisation and phagocytosis of causal pathogens 2. Neutralisation of virulence factors incl endo and exotoxins 3. Immunomodulation via interaciton with complement 4. Prevention of hyperinflammatory responses