Weekly blog - Overwhelming Post Splenectomy Infection (OPSI)

I couldn't do better than to refer you to the great "Care of the Asplenic Patient" NEJM article from July 24... Get that here.

What was discussed was this (?false!) belief that ceftriaxone ought not be used in patients with sickle cell anemia due to a fear of antibiotic associated hemolysis.  I do believe that rare drug adverse events do exist -- but I'm uncertain we should en masse change our practices over the fear of rare events.

There certainly is a literature on ceftriaxone induced hemolytic anemia (drug induced hemolytic anemia, DIHA), occuring in sickle cell anemia patients as well as other patients (see here).  In this reference lab, of 169 cases of drug induced hemolysis reported there were 15% of them due to CTX -- the proportion due to CTX increasing as the rates of CEFOTETAN use went down.  In fact, CTX was the number two reported agent for DIHA!

PIP-TAZO has also been linked to drug induced severe and acute hemolysis... (see here) ... oh, and in the report of ceftriaxone I referenced above -- Guess who was number one cause?  PIPERACILLIN.

... also there are case reports for the FLUOROQUINOLONES as well... (see here)

The key is that these are RARE events given the frequency in which these agents are used. The keen clinician is mindful that they exist but does not knee-jerk avoid very useful agents for potential fatal infections out of a fear of rare events.

People can die from adverse reactions to CT contrast (example).  This doesn't mean that we shouldn't use CT contrast.  Rather it means that CT contrast should be used when the expected benefit of contrast exceeds the risks.

***

As discussed, fluoroquinolones carry they own risks -- particularly in sickle patients who may be receiving QTc prolonging medications (think torsades) like methadone or other narcotics.  They may also (in our setting) be associated with an increased risk of C. difficile.

Piperacillin-Tazobactam seemingly would cover most S. pneumoniae but I really cannot say how effective it would be against AMPICILLIN resistant Neiserria species or beta-lactamase negative ampilillin resistant (BLNAR) H. infuenzae, which would likely be resistant. Ceftriaxone has been used in Neiserrial and BLNAR infections.

So, I would agree with the uptodate article on the issue (link) -- ceftriaxone should proabably be the "go to drug" in asplenic patients with sickle-cell anemia and probable infection in the asplenic host.  

With a careful observation for worsening hemolysis and consideration of an early change in the face of the rare, but severe, side effect of intravascular hemolysis.  And an attention to proper dosing in the very young or very underweight individuals.

Weekly blog -- Harms of benzodiazepines in the elderly...

In Choosing Wisely,  The Canadian Geriatrics Society advised physicians and patients to refrain from using benzodiazepines as first-line treatment for insomnia in older adults (link). 

To quote them:

"The number needed to treat with a sedative-hypnotic for improved sleep is 13, whereas the number needed to harm is only 6"

Adverse events include:

• Cognitive impairment (link)

• Hip Fracture
• In this cohort study there was a 10-40% increased rate of hip fracture in users of sedative-hypnotics including benzodiazepines and non-benzo sedative hypnotics (link).  
• Shockingly the population attributable risk may be as high as 8.2%! (link)
• Respiratory events in patients with chronic lung illnesses
• In this cohort (Ontario) patients with COPD who received benzos had an increased rate of adverse respiratory events (link)
• Increased risk of death in this population (link)
• All cause mortality:
• In this cohort, sleeping pills were associated with a 3 fold increase of death (link).
• Similar effect size in this cohort (link)... 4 deaths per 100 people over 7.6 years.
• Pneumonia and death in age <60 (link)
• Car accidents
• FDA advisory of sedative/hypnotics and car accident risk (and need to reduce dose) (link)

Below is a must read for those who are interested in reducing benzodiazepine use in the frail elderly...I think it is a real example of success in intervening against potentially (probably) inappropriate prescription drug use.

Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial 

(And yes, before anyone sends me angry emails, I know that maybe INSOMNIA is associated with all of these adverse events and that the sedatives may be the "innocent bystander"...  To you, I can only say, "primun non nocere"... Show me the randomized controlled trial...)

Weekly blog - Liver lesions (to aspirate or not to aspirate)

Aspirations of liver lesions... it’s not just about their hopes and dreams.

Today in rounds we discussed a case of liver lesion and debated as to whether or not it should have been drained.  In the case of a cystadenocarcinoma you may want to avoid drainage to prevent disease dissemination; in contrast, drainage of a pyogenic liver abscess is a common therapeutic and diagnostic procedure. 

Here’s a review on how to differentiate cystadenocarcinoma from liver abscess: https://webvpn.mcgill.ca/http/www.sciencedirect.com/science/article/pii/S0039610910000393

The bottom line is that a cystadenocarcinoma that secretes mucin can be difficult to distinguish from a pyogenic abscess based on imaging.  

It can be helpful to identify patient risk factors for pyogenic abscess. In a susceptible patient presenting with infectious symptoms, you will likely aspirate the lesion to avoid unnecessary surgical intervention and the associated morbidity and mortality.

Host factors and susceptibilities for pyogenic liver abscess:

·     *  delayed treatment of intraabdominal processes (appendicitis, diverticulitis, cholecystitis)

·     *  biliary obstruction, stenting, or manipulation

·     * diabetes/immunosuppression/congenital immune deficiency (i.e. Chronic Granulomatous Disease)

·     * endocarditis or IVDU (leading to hematogenous spread)

The original 1946 NEJM article describing the “five ways in which pyogenic organisms invade the liver”:

https://webvpn.mcgill.ca/http/www.nejm.org/doi/pdf/10.1056/NEJM194603212341203

See previous blog on this issue here and my color rendition of the mechanisms

Microbiology (not an exhaustive list):

·         Polymicrobial, gram negatives and anaerobes

·         S. milleri /S. anginosus, S. aureus, S.pyogenes (and other gram positive cocci),

·         Klebsiella pneumonia (think of this pathogen in patients with diabetes, particularly with monomicrobial abscess with metastatic spread to other organs)

·         Other: Candida, Tuberculous, Burkholderia. Amebiasis.

Some diagnostic pearls pertaining to liver abscess:

·         Initially, an abscess may be hyperechoic and indistinct; but with maturation and pus formation, it becomes hyperechoic with a distinct margin. Thick pus or multiple small lesions might be confused with solid lesions

·     

    Peripheral enhancement on CT is VERY helpful!

·         Don’t forget to do blood cultures (non invasive, though sensitivity only about 40%)

·   

I   Infectious symptoms may only occur late. “Large infections with bacteria of modest virulence can develop with only subtle symptoms.”  To illustrate this point, here is a case of pyogenic liver abscess, caused by strep mitis:

https://webvpn.mcgill.ca/http/www.sciencedirect.com/science/article/pii/S147330991370166X

Any discussion of indolent abscess should also include a nod to S. milleri group organisms.

To learn about klebsiella pneumonia liver abscess (a 2013 review of the European literature with some illustrative case reports from the journal Infection):

https://webvpn.mcgill.ca/http/download.springer.com/static/pdf/639/art%253A10.1007%252Fs15010-013-0408-0.pdf?auth66=1405612498_f6a242bfba61dae025ccc76b7078bb4b&ext=.pdf

See the previous blog on this particular entity here. 

Finally, a “NEJM case records of the Massachusetts General Hospital”, looks at a case of liver abscess (read more to find out what interesting pathogen was involved in this case!)

https://webvpn.mcgill.ca/http/www.nejm.org/doi/full/10.1056/NEJMcpc069017

- egm and tcl

Weekly Blog - Whipple's disease with amyloidosis

Since it was mentioned I thought it would be worth a quick note on Whipple's disease:

See review NEJM here.

It is a disease mostly described in men (>85%)

The majority of patients have:
* Weight loss (>90%)
* Diarrhea (80%)
* Arthritis (70%)

Neurologic symptoms or the classic occular findings are seen in 33% and <10% respectively.

"Roughly 15% of patients with Whipple's disease do not have the classic signs and symptoms of the disease"

Diagnosis is made through:
* PAS staining of GI biopsies -- usually several are required
* PCR on tissue or blood/CSF can also be positive
* Electron microscopy can also be used

Treatment:
CEFTRIAXONE induction, TMP/SMX consolidation
Alternative: DOXYCYCLINE

Note that discussed patient also had evidence of a monoclonal light chain in the urine prompting suspicion of amyloidosis (not seen on biopsy of the gut, nor in the serum).

There are several case reports of Whipple's disease being associated with amyloidosis (particularly with renal involvement -- i.e. nephrotic syndrome; also presenting with wasting illness without diarrhea like that discussed)

This case has the full report if you are a McGillian -- here.

Also see here, here, here and here .  (many not available online)

Yes, the patient may not have Whipple's disease -- but it is curable and compatible with the illness (which primary amyloidosis, the alternative, is not in the specific patient's condition).