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
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
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
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
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.