Flea Bytes: Oral Edoxaban in VTE Prophylaxis in Cancer Patients

Open label non-inferiority trial of 1046 cancer patients (1050 randomized). Non-inferiority margin of 1.5 (HR 1.5), appears to have been randomly decided upon. Expected event rate of 20%, but had an event rate of 13%. Primary endpoint combined VTE and bleeding events which had a HR of 0.97. However, edoxaban improved VTE risk (not reaching statistical significance) by reducing DVTs, but not pulmonary embolism. Further, it had more bleeding, but the increased bleeding event severity was mostly category 2, while category 3 bleeding was similar. This was mostly upper GI bleeding and the authors note in the discussion section that it was mostly in patients with GI cancers and whined that the dalteparin bleeding rate was lower than previously reported.

My takeaway – edoxaban seems like a reasonable option for VTE prophylaxis in cancer patients, although it might increase bleeding risks.

Source: N Engl J Med 2018; 378:615-624


Flea Bytes: HHV-6 Encephalopathy

HHV-6 reactivation is one of the most common causes (in 30-70% of patients) of encephalitis in allo-SCT. It is a ubiquitous viral infection that remains latent and can reactivate after transplant.

Risk factors: HLA mismatch, T-cell depletion therapy, treatment with glucocorticoids, and the use of cord blood as a source of stem cells; 90% of cases of HHV-6 reactivation occur in patients who with cord-blood transplants.

Encephalitis presents as subacute confusion, but some may have a more progressive course. Anterograde amnesia, personality changes, irritability and seizures. SIADH is common.

CSF analysis shows mild lymphocytic pleocytosis and protein elevation.

Treatment is based on in-vitro susceptibility testing and foscarnet is therapy of choice. Can add ganciclovir if not clinically improving. But need to monitor closely for side effects including bone marrow suppression and electrolyte derangement which can predispose to seizures. Alternative therapy is cidofovir, but watch out for nephrotoxicity.  Duration is 3-6 weeks and you shouldn’t monitor PCR levels to shorten treatment duration.

Notes from: N Engl J Med 2018; 378:659-669

Flea Bytes: Duration of NG Tubes

  • You should consider a PEG in patients who are likely to require > 4-6 weeks of feeding and there is some evidence that you should consider it at 14 days
  • Polyurethane NG tubes (Dobhoff) should be replaced every 2 weeks due to the effects of gastric acid.
  • Long term NG/NJ tubes can be kept in place for 4-6 weeks

Flea Bytes: Treating Aspiration Pneumonia

For most patients: Ampicillin/Sulbactam is sufficient for oral aerobe/anaerobic coverage

For penicillin allergic patients: Clindamycin monotherapy covers oral aerobes/anaerobes

For hospital-acquired aspiration PNA: Coverage of aerobic bacteria, especially GPC and GNR are more important than anaerobes: Pip/Tazo or meropenem monotherapy

In patients with high risk factors for MRSA, can add an agent with MRSA activity but if MRSA is not detected, this agent should be discontinued

Flea Bytes: Heavy Metal Poisoning

How do patients with heavy metal toxicity present?

Here is a quick table:

Lead: Abdominal pain, irritability, fatigue, anemia, (confusion, seizure, encephalopathy at very high levels)

Cadmium: Interstitial Nephritis

Acute: Nausea, vomiting, severe watery diarrhea.

Chronic: Distal polyneuropathy


Acute: Chest pain, cough, dyspnea

Chronic: Mild neuropsychiatric symptoms with predominant tremor

Flea Bytes: Polymixin/Meropenem Synergy

Meta-analysis found in vitro synergy.  Especially in A baumanii. Mechanism unclear

Synergy testing can be done on isolate if available

Can not necessarily infer in vivo synergy (Beta-lactam/aminoglycoside synergy is demonstrated in vitro but NOT in vivo for example).

Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems. Antimicrobial Agents and Chemotherapy. October 2013 Volume 57 Number 10. p.5104 – 5111.

Tidings from the Citadel: Warfarin in Dialysis

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis – Mitesh Shah et al. Circulation. 2014;129:1196-1203.

A retrospective cohort study

Population based cohort of patients > 65 years who were admitted in Canada – Quebec and Ontario with a primary or secondary diagnosis of atrial fibrillation. Used ICD-9/10 codes to determine diagnosis and complications such as bleeding and stroke complications. Drug prescriptions were identified by database in Canada where patients > 65 have prescription benefit. Warfarin use was identified by a filled prescription within 30-days of AF diagnosis

626 dialysis patients and 204,210 nondialysis patients. Did not separate by stages of CKD, but rather HD or non-HD. Dialysis patients were younger, male, CHF, HTN, DM, CAD, and bleeding history.

Dialysis vs Non-Dialysis: CHADS2 >/= 2: 72% versus 55% (indication for anti-coagulation); HAS-BLED >/=3: 85% versus 25%. Similar rates of warfarin prescription (46% vs 51%)

image (3)

In non-dialysis patients, warfarin users had a lower incidence of stroke (2.19 vs 2.51/100 person-years)

In dialysis patients, stroke incidence was similar for warfarin and non-warfarin users: 3.37 versus 2.91/100 person-years.

After adjusting for confounders – warfarin use had a HR of 1.14 in diaylsis patients. While in non-dialysis patients had a HR 0.87 with warfarin use.

After adjusting for confounders, warfarin use, was associated with a 44% higher risk for bleeding event in dialysis patients and 19% higher risk in nondialysis patients.


image (4)