Draft

124  Boared Review Locke

124.1 Summary

  • SEEK Board Review 10-13-21
  • Other options?
  • Cp-Kpn (Carbapenemase-producing Klebsiella Pneumoniae)
  • How does Ceftazidime-Avibactam work?
  • What is ceftaroline and how is it used?
  • What are the types of beta-lactamases?
  • GNR Bacteremia with CTX resistance – abx?
  • Methotrexate, HyperCa neurotoxicity
  • Sarcoidosis Small Fiber Neuropathy

124.2 Slide outline

124.2.1 Slide 1

  • SEEK Board Review 10-13-21
  • Locke ### Slide 2
  • TODO: No text extracted from this slide. ### Slide 3
  • TODO: No text extracted from this slide. ### Slide 4
  • Other options? ### Slide 5
  • Cp-Kpn (Carbapenemase-producing Klebsiella Pneumoniae)
  • KPC is a type of beta-lactamase encoded on plasmids
  • Carbapenems are beta-lactams
  • KPC also confers resistance to cefepime, quinolones, TMP-SMX
  • KPC has been found in Klebsiella and PsA
  • Nosocomial; selection thought to have resulted from failure to clean medical equipment (repeat broad spectrum antibiotic exposures) ### Slide 6
  • How does Ceftazidime-Avibactam work? ### Slide 7
  • How does Ceftazidime-Avibactam work?
  • Ceftazidime – 3rd gen ceph but + ~85% PsA coverage, poor anaerob coverage.
  • Avibactam – beta-lactamase inhibitor (broader than tazobactam)
  • Other options:
  • Meropenem-Vaborbactam, colistin (polymixins) ### Slide 8
  • What is ceftaroline and how is it used? ### Slide 9
  • What is ceftaroline and how is it used?
  • 5th generation Cephalosporin with MRSA/VRSA activity and good gram positive activity. GNR coverage is similar to CTX
  • Hydrolyzed by KPC ### Slide 10
  • What are the types of beta-lactamases?
  • ESBL
  • Carbapenemases (subtype of ESBL)
  • AmpC (inducible, subtype of ESBL)
  • How to recognize:
  • GNR – resistant to CTX
  • +/-S to Cefepime (reported)
  • S to meropenem
  • R to Erta/Mero
  • SPACE/SPICE-M organism – will appear susceptible but in fact will not be. Can be CTX sensitive on report.
  • Treatment
  • Cefepime if susceptible, Mero if not.
  • NOT Zosyn.
  • Ceftaz-Avibact;
  • Mero-Vaborbact;
  • Colistin
  • Carbapenem (induces, but not hydrolyzed); Cefepime (doesn’t induce much. But is hydrolyzed so can be ok). NOT Zosyn, CTX.
  • Serratia marcescens, Providencia, PsA, Citrobacter, Enterobacter (40%), Morganella morganii ### Slide 11
  • GNR Bacteremia with CTX resistance – abx? ### Slide 12
  • GNR Bacteremia with CTX resistance – abx?
  • NOT AmpC in this study (unless also present with another ESBL, 10%) ### Slide 13
  • TODO: No text extracted from this slide. ### Slide 14
  • TODO: No text extracted from this slide. ### Slide 15
  • Methotrexate, HyperCa neurotoxicity
  • Weekly MTX: Headache, fatigue, malaise, impaired ability to concentrate
  • CNS folate metabolism disruption.
  • Can get acute stroke/seizure-like presentation, but more common with high (chemo) or intrathecal dosing.
  • Hypercalcemia: anxiety, irritability, depression, cognitive impairment
  • confusion, stupor, and coma if severe ### Slide 16
  • Sarcoidosis Small Fiber Neuropathy
  • Destruction of thin myelinated and unmyelinated fibers (nociception, heat, autonomic function)
  • +Allodynia
  • Autonomic dysfunction rarely occurs alone.
  • Exclude DM, B12 def, thyroid
  • NCS is normal; biopsy specific but not sensitive.
  • Incidence not well known
  • Unique: Resistant to pred & methotrexate - ?IVIG and TNF-alpha; symptom management (capsaicin) ### Slide 17
  • TODO: No text extracted from this slide. ### Slide 18
  • TODO: No text extracted from this slide. ### Slide 19
  • How does Dabigatran work? ### Slide 20
  • How does Dabigatran work?
  • Direct thrombin inhibitor
  • Not Xa inhibitor!
  • Direct
  • Indirect
  • (mediated by ATIII)
  • Xa inhibition
  • Rivaroxaban
  • Apixaban
  • Edoxaban
  • Enoxaparin
  • Fondaparinux
  • Thrombin inhibition
  • Dabigatran
  • Bivalrudin
  • Argatroban
  • Unfractionated Heparin ### Slide 21
  • TODO: No text extracted from this slide. ### Slide 22
  • Heparin
  • Thrombin + Xa inhib
  • Protamine
  • Time based:
  • Immediate 1U/100U hep
  • …
  • 120 minutes 0.25u/100u hep
  • Enoxaparin/Dalteparin
  • Thrombin inhib
  • <4h – 1mg per 1mg
  • 4-8 – 0.5 mg per 1mg
  • Fondaparinux
  • 4F-PCC
  • 50u/kg
  • Dabigatran
  • Idaracizumab
  • 5 grams IV
  • Apixaban
  • Xa inhib
  • 4F-PCC or Andexanet
  • 50 u/kg; 400mg then 4mg/min
  • Rivaroxaban
  • 50 units/kg; 800 u then 8mg/min
  • Edoxaban
  • 4F-PCC (not andexanet)
  • 50 units/kg
  • Warfarin
  • Vit-k epoxide-reductase inhib
  • Vit K; FFP; 4F-PCC
  • Vit K: 2.5-10 mg (use INR)
  • FFP: 15 ml/kg
  • PCC: 2-4 25u/kg, 4-6 35u/kg, 6+ 50u/kg ### Slide 23
  • Idarucizumab (Praxbind)
  • Dabigatran (Pradaxa) – eliminated by the kidneys
  • Fab fragment (antibody) that binds dabigatran w/ 350x better affinity than thrombin. ### Slide 24
  • Andaxant Alfa
  • Decoy Xa (molecular similar) – Xa inhibitors bind to it instead
  • Unlike factor Xa, it does not convert prothrombin to thrombin
  • Tested in (direct) Xa inhibitors – Edoxaban, Apixaban, Rivaroxaban
  • Probably works in enoxaparin too, but not formally evaluated ### Slide 25
  • Protamine
  • Big positively charged molecule – forms a stable salt with negatively charged heparin
  • If given alone, protamine is an anticoagulant
  • If given w/ heparin – will pair up and make the salt.
  • Also pairs up with enoxaparin/dalteparin, but not quite so effectively. ### Slide 26
  • 4F – PCC (K-Centra)
  • Prothrombin complex concentrate
  • Factors 10, 9, 7, 2; and protein C and S.
  • Smaller volume infusion than FFP (15-20mL/kg) ### Slide 27
  • Your patient is bleeding; found down. Lab test to assess AC?
  • Apixaban: Anti-Xa levels
  • Dabigatran: Thrombin time, aPTT. NOT INR
  • Edoxaban: Anti-Xa levels, INR
  • Rivaroxaban: Anti-Xa levels, INR (50% will have anticoag w/ normal) -> not sufficient to exclude. ### Slide 28
  • TODO: No text extracted from this slide. ### Slide 29
  • TODO: No text extracted from this slide. ### Slide 30
  • TODO: No text extracted from this slide. ### Slide 31
  • TODO: No text extracted from this slide. ### Slide 32
  • Path
  • Tb – caseating granulomas
  • Yeast forms:
  • Cocci – large spherules
  • Histo – small round spherules within macrophages
  • Blasto – thick capsule, daughter-buds with broad base
  • Crypto – similar, but thin base
  • Sporothrix – small, cigar shaped. ### Slide 33
  • TODO: No text extracted from this slide. ### Slide 34
  • Locations ### Slide 35
  • Locations
  • Histo
  • Blasto
  • Cocci ### Slide 36
  • Dimorphic fungi
  • Blasto – never colonizer; mainly endemic Ohio and Mississippi river valleys -> grows in moist, decaying organic matter; outbreaks after floods.
  • Route: inh. All get PNA, then 20% skin, 5% bone, 2% cns
  • 4-8 weeks since inh.
  • Blast: asymptomatic, pneumonia, extrapulmonary disease
  • Ampho (if severe) -> Itra ### Slide 37
  • Treatments
  • Coccidiomycosis
  • Fluconazole (Ampho if severe)
  • Blastomycosis
  • Itraconazole (Ampho if severe)
  • Histoplasmosis ### Slide 38
  • TODO: No text extracted from this slide. ### Slide 39
  • TODO: No text extracted from this slide. ### Slide 40
  • Primary graft dysfunction
  • Within 72h of transplant usually. Assessed at 24/48/72h
  • Ischemia reperfusion -> ARDS presentation (Diffuse alveolar damage)
  • Dx of exclusion of other causes of ‘ARDS’, PCWP for congestion, TEE for pulm venous stenosis.
  • Predisposing conditions
  • Donor: smoking and aspiration/trauma/undersize
  • Surgery: cardiopulmonary bypass, large volume transfusion, delayed closure, prolonged ischemic times, increased reperfusion fio2
  • Recipient: abnormal body weight, pulm htn, COPD/CF
  • Supportive care, LTVV, Abx, iNO/PG, ECMO.
  • Retransplant bad outcomes, not done. ### Slide 41
  • PGD consequences
  • Increased mortality at 1 year
  • Increased risk of developing BO-type CLAD
  • CLAD chronic lung allograft dysfunction
  • BO bronchiolitis obliterans syndrome
  • No increase in risk of future acute cellular rejection or infection
  • Not clear if humoral rejection risk influenced ### Slide 42
  • TODO: No text extracted from this slide. ### Slide 43
  • TODO: No text extracted from this slide. ### Slide 44
  • What things cause PaO2-SpO2 gap? ### Slide 45
  • What things cause PaO2-SpO2 gap?
  • SpO2 absorption spectrum @ 660 and 940 nm.
  • Hemoglobinopathy changes absorption spectrum
  • iStat sometimes don’t actually do co-oximetry – they calculate a predicted oxygen saturation.
  • Need “co-oximetry” - measure oxy-, deoxy-, carboxy-, and methemoglobin ### Slide 46
  • Hemoglobinopathies
  • Sickle hb no change in absorption spectrum
  • Carboxyhemoglobinemia
  • Methemoglobinemia
  • 95-100% apparent SpO2
  • 85% apparent SpO2
  • COHb O2Hb
  • Met-Hb blue absorption ### Slide 47
  • Physiology
  • Oxidizing agent (electron acceptor) takes Fe++ (Ferrous) to Fe+++ (Ferric) metHb
  • Normally, reducing agent (CyB5R) converts it back
  • Met-Hb, like CO-Hb, binds O2 more tightly. Shifts O2-hb to the left
  • SpO2 based only on the color of the molecule
  • O2 Physiology identical to COHb ### Slide 48
  • Why did this patient get Met-Hb?
  • Oxidizing Agents:
  • Dapsone
  • Antimalarials (CQ, Quinones)
  • Topical anesthetics
  • iNO, nitrites, nitrates
  • Anilene Dyes
  • Metoclopramide ### Slide 49
  • How to treat?
  • Reducing Agents:
  • Methylene blue -> cofactor in Fe+++ to Fe++ transition.
  • Beware in G6PD deficiency this won’t work. ### Slide 50
  • What is Sodium nitrite/thiosulfate used for?
  • Cyanide poisoning options:
  • Hydroxycoabalmin – first line, directly binds. 70mg/kg. Interferes w Co-ox
  • Induction of methemoglobinemia with amyl/sodium nitrite, which can then be reduced. Don’t do this if CO-Hb/Smoke (further reduce O2-Hb availability)
  • Sulfur donors e.g. sodium thiosulfate turn cyanide to thiocynates which are renally eliminated.
  • 1 and 3 are recommended.

124.3 Learning objectives

  • SEEK Board Review 10-13-21
  • Other options?
  • Cp-Kpn (Carbapenemase-producing Klebsiella Pneumoniae)
  • How does Ceftazidime-Avibactam work?
  • What is ceftaroline and how is it used?

124.4 Bottom line / summary

  • SEEK Board Review 10-13-21
  • Other options?
  • Cp-Kpn (Carbapenemase-producing Klebsiella Pneumoniae)
  • How does Ceftazidime-Avibactam work?
  • What is ceftaroline and how is it used?

124.5 Approach

  1. TODO: Outline the initial assessment or decision point.
  2. TODO: Outline the next diagnostic or management step.
  3. TODO: Outline follow-up or escalation criteria.

124.6 Red flags / when to escalate

  • TODO: List red flags that require urgent escalation.

124.7 Common pitfalls

  • TODO: Capture common errors or missed steps.

124.8 References

TODO: Add landmark references or guideline citations.

124.9 Slides and assets

124.10 Source materials