Fecal Transplant versus Fidoxamicin for Recurrent C Difficile

Fecal transplant (FMT) is increasingly used to treat recurrent clostridium difficile infections (rCDI) with reported cure rates of 70-90%. FMT’s efficacy has been studied in prospective and observation studies, however, it is unclear how it performs against fidoxamicin, a newer antibiotic used in the initial presentation and recurrence of CDI.

FMT is probably more efficacious than fidoxamicin and vancomycin for rCDI. My main concern with this study is that it was unblinded as to who received the FMT and could potentially influence the difference in microbiologic vs symptomatic cures with FMT. Interestingly, more patients treated with antibiotics had microbiologic cures than symptomatic cures, (vancomycin 31% microbiologic cure while only 19% clinical cure).

Fecal Microbiota Transplantation is Superior to Fidaxomicin
for Treatment of Recurrent Clostridium difficile Infection, Gastroenterology (2019)

OPAT for Complicated Staph Infections

Among patients discharged with OPAT for complicated staph infections, 1/3 had an adverse event and nearly 2/3 were re-admitted within 90 days. Patients discharged to a skilled nursing facility (SNF) were lost to follow up at higher rates than those discharged with home care services (HCS) and had higher incidence of line complications. What surprised me was that the ID clinic only received labs from 44% of patients at SNF and 53% at HCS. But at the end of the day, both discharge locations had similar rates of “favorable outcomes”, 61% vs 70%. The SNF vs home care comparison maybe confounded because older and sicker patients are more likely to be sent to SNF/SAR

We often discharge patients on long courses of parenteral antibiotics for Staphyloccus auerus infections and we must recognize they are likely to face significant adverse events and complications. It is unclear if this is due to the severity of the underlying infection, and more importantly, could it have been prevented with closer inpatient monitoring. This study should give you pause when sending patients to SAR/SNF on long term IV antibiotics.

Open Forum Infectious Diseases, Volume 5, Issue 11, 1 November 2018, ofy274

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

Maester’s Collection: Cushing Syndrome

• Central obesity, arterial hypertension, proximal muscle weakness, diabetes, oligomenorrhea, hirsutism, thin skin, and ecchymosis
• Today, obesity is common. Anti-androgenic effects of Cushing syndrome can help differentiate it from obesity
  • +LR thin skin 112
  • +LR osteopenia 18
  • +LR ecchymoses 4
  • All 3 have a specificity of 95%
• Prevalence of Cushing in obese/metabolic type patients 0.2%
  • 24,000 cases of Cushing/12 million patients with metabolic syndrome = 0.2%
• 24 hour urinary free cortisol
  • 2-forms: 1) unbound to protein or 2) cortisol unconjugated to sulfuric or hyaluronic acid
  • Unbound cortisol is filtered and reabsorbed. 3% remains in urine.
  • Should measure 24-hour urine creatinine with cortisol to ensure adequate collection
    • Repeat if creatinine is less than 1.5g/day for men and 1g/day in women
  • 24-hour urine cortisol > 62mg/day has +LR 11
• Dexamethasone Suppression test is used to differentiate ACTH dependent from ACTH independent Cushing syndrome.
  • This is now done by directly measuring ACTH levels
  • Should not be used to diagnose or screen for Cushing syndrome
    • Obese patients with depression will fail to suppress cortisol in response to dexamethasone challenge
• For Cushingoid exam, but low or zero urinary free cortisol and suppressed ACTH levels suggests exogenous steroid and should prompt a review of medications.
• ACTH-dependent Cushing syndrome can be due to pituitary secretion from an adenoma or ectopic secretion from a malignant source – typically in the chest.
• Some experts recommend always doing petrosal sinus sampling due to the high prevalence of non-functioning pituitary adenomas and mortality associated with surgery. Some series report the prevalence of asymptomatic pituitary adenomas as high as 15-40%. Mortality associated with transsphenoidal micro-adenectomy is 1%.
• ACTH-independent Cushing syndrome is usually caused by an adrenal neoplasm.
  • Characteristics of benign tumors: small (<5cm), <10 Hounsfield units, and have > 60% contrast washout at 15 minutes.
    • Benign tumors can be treated laparoscopically, while malignant tumors typically are resected with an open technique.

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

Arsenic:
Acute: Nausea, vomiting, severe watery diarrhea.

Chronic: Distal polyneuropathy

Mercury:

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

Patients
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%)

Stroke
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.

Bleeding
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.