Day #43 - Endocarditis

Today we discussed a great case of subacute bacterial endocarditis which presented as renal failure, uremia, and life threatening hyperkalemia. We discussed the approaches to altered level of consciousness and hyperkalemia. We also briefly discussed the approach to renal failure.

I wanted to touch upon the diagnosis of endocarditis. Endocarditis is a clinical and microbiological diagnosis which is established using epidemiologic criteria. The criteria are called the Modified Duke Criteria. They include:

Major Criteria

Microbiologic:
Positive blood cultures (>=2) with an organism that classically causes endocarditis (viridans group streptococci, staphylococcus aureus, enterococcus, HACEK organisms)
OR
Persistantly positive (>=3 or >=2 12h apart) for another organism

Echocardiologic:
Vegetation on valve not otherwise explainable or dehiscence of mechanical valve or abscess

OR

Clinical: *NEW* (not worsening) regurgitant murmur

Minor Criteria

• Predisposition -- known pre-existing valvular disease or IVDU
• Fever
• Evidence of vascular phenomenon -- septic emboli, mycotic aneurysm, Janeway lesions,
• Immunologic: glomerulonephritis (like this case), positive RF, roth spots, Osler nodes,
• Microbiologic: Blood culture not meeting major
• Echocardiographic not meeting major

Diagnosis: 2 Major, or 1 major 3 minor, or 5 minor

The ACC has updated guidelines on the management of valvular heart disease including endocarditis and endocarditis prophylaxis. These address the diagnostic algorithm and treatment in more detail.

Endocarditis

We discussed endocarditis today. I will take this opportunity to 'show off' the search function of the blog and direct you here.

Duke Criteria:

Major Criteria

Microbiologic:

Positive blood cultures (>=2) with an organism that classically causes endocarditis (viridans group streptococci, staphylococcus aureus, enterococcus, HACEK organisms)
OR
Persistantly positive (>=3 or >=2 12h apart) for another organism

Echocardiologic:
Vegetation on valve not otherwise explainable or dehiscence of mechanical valve or abscess

OR

Clinical: *NEW* (not worsening) regurgitant murmur

Minor Criteria

• Predisposition -- known pre-existing valvular disease or IVDU
• Fever
• Evidence of vascular phenomenon -- septic emboli, mycotic aneurysm, Janeway lesions,
• Immunologic: glomerulonephritis (like this case), positive RF, roth spots, Osler nodes,
• Microbiologic: Blood culture not meeting major
• Echocardiographic not meeting major

Diagnosis: 2 Major, or 1 major 3 minor, or 5 minor

The ACC has updated guidelines on the management of valvular heart disease including endocarditis and endocarditis prophylaxis. These address the diagnostic algorithm and treatment in more detail.

Day #299 - Enterococcal Prosthetic Valve Endocarditis

Great case. I have previously blogged about the diagnosis of endocarditis here and here.

Patient with multiple prosthetic valves develops sepsis in the context of an enterococcal bacteremia. Highly suspicious though non diagnostic echo for PVIE. Treated with VANCOMYCIN ("penicillin allergy" is a pet peeve of mine) and GENTAMICIN (for synergy). The evidence for synergy is not totally supported by clinical experience. Nephrotoxiciy is common but similarly has not been shown to impact mortality. The combination of VANCOMYCIN with an aminoglycoide increases the risk of nephrotoxicity.

We also reviewed aminoglycoside ototoxicity -- presenting either as sensory-neuro hearing loss or vestibulary dysfunction.

This patient developed renal failure presumably related to ATN from the VANCO+GENT; however, one can get a glomerulonephritis in endocarditis.

There is evidence that AMPICILLIN plus CEFTRIAXONE (which usually has no enterococcal coverage) can be used effectively in the treatment of enterococcal endocarditis.

Day #252 - Infective Endocarditis (Staphylococcus Aureus)

Today we heard a case of a patient with a known history of injection drug use who presented with multiple swollen joints, in the context of a persistant staphylococcal bacteremia. The patient also had a history of previous endocarditis and on exam had evidence of moderate-severe tricuspid regurgitation.

I have reviewed the diagnostic criteria for endocarditis here.

I have previously blogged about staphyloccocal bacteremia here. I will re-iterate that for methicillin sensitive staph aureus vancomycin is INFERIOR to beta-lactam therapy.

Some newer evidence suggests that the risk of using adjuvant gentamicin in native valve staphylococcal bacteremia/endocarditis is greater than the benefit.

An interesting concept, which I am now going to endorse because it is inexpensive and relatively simple, is continuous cloxacillin infusion as opposed to intermittant infusion. In this study the 30 day microbiologic cure was 94% in the CI group as opposed to 79% in the II group (ARR 15%, NNT 8).

There have been several studies looking at treatment options in injection drug users. Long term antibiotic therapy requires indwelling lines and this usually mandates extended hospitalization or "confinement" if ongoing drug use is a concern. These two studies (larger study, smaller study) have evaluated quinolone (ciprofloxacin, though today levofloxacin or moxifloxacin would likely be even more effective) combined with rifampin in right sided IE. These are small studies, so they shouldn't influence practice in general -- but in certain cases may be the only option.

Day #322 - Enterococcal Endocarditis

This patient presented with stroke. This article reviews stroke in IE. This related article reviews the neurologic manifestations of IE.




An original article by Osler on IE!



Some key points:
Mitral Valve IE ~ 10% stroke rate
Mortality is high -- 35% in hospital 52% at one year
Early antibiotic therapy reduces neurologic complications


I have previously blogged about infective endocarditis (see here) including enterococcal endocarditis. The first post goes over the Duke Criteria.



Indications for Surgical Treatment of IE (Native Valve):

• Development of heart failure
• MR/AR with dilating LV, or development of pulmonary hypertension
• Fungal IE or that caused by highly resistant organisms (think of it in MRSA)
• Patients with heart block, cardiac abscess, abnormal chamber-chamber connections
• Recurrant emboli despite ABX
• Class IIb -- large vegetations

Enterococcal Endocarditis

We saw a case of aortic and mitral valve enterococcal endocarditis.

Previous endocarditis blogs here with associated links.

While not really studied, there are some limited case reports or in vitro data for the possibility of:

• Daptomycin (also retrospective review in bacteremia here)
  
• Linezolid (and in general review of linezolid in IE here)
• Ceftobiprole (NB it lost its FDA approval in April 2010!)
  

Other options are reviewed here.

Though any of the above agents should primarily be used in the context of clinical trial or 'dire cicrumstances'

Day #92 - "I don't know"

Wow. What a great case. It isn't often that I truly throw my hands up and say that "I don't know" but this was one of them.

But I hope the exercise in reasoning was useful for you. I think we demonstrated an approach that was safe, cost-effective, and broad in going through the history and physical exam.

Dr. Gold previously spoke about meningitis (bacterial) and that talk is available here.

In approaching a patient with multiple infarcts we need to consider the following differential:

• Emboli - Arising from the heart or great vessels. One possibility is subacute bacterial endocarditis, particularly given the history of night sweats. I think this patient needs blood cultures drawn with blind subculturing (endocarditis blood cultures) to look for unusual pathogens like brucella. I also think he needs a trans-esophogeal echo looking for a cardiac source including a bubble study to exclude PFO. This can also look at the aortic arch.
  
• Ischemia -- Either bad luck from uncontrolled risk factors, or genetic stroke syndrome like CADASIL, Fabry's or MELAS, or thrombophilia like antiphospholipid antibody syndrome, ATIII deficiency or hyperhomocysteinemia. I would exclude thrombophilia. As a last resort I would look into genetic testing. Night sweats don't fit with ischemia.
  
• Vasculitis (Night Sweats would fit with this too)
  
  • Primary:
    
    • Primary CNS angiitis
    • GCA/Takayatsu, polyarteritis nodosa (patient has Hep B!)
      
  • Secondary due to:
    
    • Infection:
      
      • Syphilis always needs to be considered in young patients who present with stroke like syndromes.
      • HIV can do this -- though he is suppressed.
        
      • CNS TB can cause this also (usually have CNS pleocytosis).
        
      • Fungal infections like cryptococcus can do this too.
        
    • Malignancy -- Angioinvasive lymphoma or lymphovascular lymphamatosis
      
• Other

If the echo is clean, I would consequently perform angiography (MRA possibly conventional) in this patient and look for evidence of vasculitis. I think given the night sweats and epidemiology that TB needs to be excluded prior to high dose steroids. I would repeat the lumbar puncture to ensure that it is still acellular (early TB can be acellular) and again send TB studies.

I would confirm whether or not he has had a mantoux. He should have one prior to immunosuppression anyways and should be treated for latent TB if this does not represent CNS TB.

I would probably scan his chest/abdomen/pelvis to look for evidence of malignancy, lymphoma or TB disease -- or something safer than the brain to biopsy and make a diagnosis.

Ultimately he may require a stereotactic brain biopsy to exclude TB and make a diagnosis. In a young man, with progressive infarcts and no other cause, I would discuss this with the patient.

TB is treatable, thrombophilia and emboli preventable, and lymphoma may be cured but CADASIL can not so we had better be sure!

Day #65 - Endocarditis

A confession -- today's case was "recycled" for your benefit -- and so is today's blog.

I have previously blogged on endocarditis, renal failure, and hyperkalemia and direct you to those sections.

Day #93 - Staphylococcus Aureus Bacteremia

Today we talked about a patient who presented with a febrile gastrointestinal illness who happened to have two diagnoses. First, a probable viral gastroenteritis acquired from his daycare aged son. Second, a concomitant staphylococcus aureus bacteremia.

I wanted to talk about the management of Staphylococcus Aureus Bacteremia. There is a good article here on the management of MRSA bacteremia.

• Never treat staphylococcus aureus in the blood as a contaminant. Like fungus in the blood, this always needs to be treated!
• The *minimum* treatment duration is 14 days (intravenous). This is for uncomplicated infections only.
  
  • Risk factors for complication:
    
    • Longer duration of illness
    • Community acquired infection
    • Persistent fever at 72h (OR 2)
      
    • Persistent positive blood culture at 96h (OR 5)
      
    • Hemodialysis patients
    • Indwelling lines or other prosthetic material
    • MRSA
    • No identifiable source for the bacteremia (i.e. no skin or line focus)
    • Blood cultures positive within 14 hours of drawing them
      
• You need to exclude bacterial endocarditis. Present in 10-13% of cases...
  
  • TEE is much more sensitive than TTE for making this diagnosis (103 patients with SA -- TEE dx endocarditis in 25%, TTE only found 7%). In patients for whom you are planning 14d therapy (particularly those who have risk factors for complication) you should probably not rely on a TTE to exclude IE.
• Can also cause pacemaker and AICD infections
• Vertebral osteomyelitis
• Septic arthritis
• Splenic abscess (persistant fever, LUQ pain)
  
• Septic thrombophlebitis (particularly with lines)
• Septic pulmonary emboli
  
• Brain abscess/meningitis/mycotic aneurysms
• Skin/soft tissue abscesses

---

Treatment:

• Ideal treatment for MSSA is with a beta-lactam like cloxacillin or cefazolin. These are superior head to head with vancomycin for the treatment of MSSA.
• Removable foci should be removed if feasible and practical to do so
• Duration depends on complications. IE 4-6 weeks. Osteo ~6 weeks.
  

Risk of Death

• 20 to 40%!
• Age
  
• MRSA (OR 9.3)
• Blood cultures positive less than 12 hours (OR 7)
• Complication (OR 9)
  

---

In medicine we often attempt to find one unifying diagnosis that explains all symptoms -- in satisfying what is known as Occam's Razor.

The important teaching point in a complicated case like this is that the patient may have multiple diagnoses and that we must keep an open mind. In response to Occam's Razor, Hickam's Dictum states that "[the patient] can have as many diseases as the damn well please".

Stenotrophomonas maltophilia

Today we saw a patient with S. maltophilia catheter related bacteremia.

Review of the microbiology of this organism here.

• Straight or slightly curved, motile gram negative rod
• Obligate aerobe, will grow best at 35 degrees
• Non-lactose fermenter, catalase positive, oxidase negative
• Will grow on blood agar and MacConkey -- and can be selected for using imipenem innoculated plates as they are carbepenem resistant organisms.

Can be found in the environment -- and in the hospital in multiple places, usually involving water. Patients who are infected are more likely to have:

• Prior antibiotic therapy
• Central venous catheters
• Neutropenia or cytotoxic chemotherapy
• ICU/Mechanical ventillation/Tracheostomy
• Malignancy or steroid use

The majority of cases are nosocomial; however, community acquired infections can occur.

Distinguishing between colonization and infection can be difficult, particularly for respiratory isolates. Bacteremia is a common presentation with an attributable mortality of up to 60%. ICU admission (APACHE more than 15), shock and thrombocytopenia are associated with mortality.

Endocarditis can occur, as can hospital acquired pneumonia, nosocomial meningitis, cellulitis and urinary tract infection.

TMP-SMX is the antimicrobial agent of choice (greater than 90% are sensitive). Combination with ticarcillin/clavulanate should be considered for serious infections. Quinolones may be a reasonable alternative in the TMP/SMX resistant or intolerant but consideration should also be given to combining them with ticarcillin/clavulinate.

Group B Streptoccal Bacteremia

Reviews here and here.

Also known as Streptococcus agalactiae, group B streptococcus is a pathogen that causes a variety of infectious syndromes. It colonizes the human GI tract and causes infection usually through a breach of the epithelial barriers.

In pregnant women it can cause choramnionitis and post-partum endometritis. In the neonate, it is a significant cause of neonatal sepsis and meningitis and this is why women are screened for carriage and given peri-partum antibiotics.

In the non-pregnant adult, it is commonly associated with:

• Bacteremia without focus (~40-50%)
• Skin/soft tissue infections (~20%)
  
• Pneumonia (~10-15%)
  
• Osteomyeltis or Septic Arthtitis (~10-15%)
• Other (Endocarditis, Peritonitis, Meningitis)
  

Diabetes is the most common underlying condition; however, other illnesses which likely pre-dispose to skin/soft tissue foci for bacterial entry including congestive heart failure is also a risk factor. Patients with underlying malignancy are also at increased risk.

Treatment includes a beta-lactam antibiotic (vancomycin in the penicillin allergic) pending sensitivities to other agents like the quinolones or clindamycin. GBS is universally penicillin sensitive at present. Source control is also important.

Day #45 - Fever of Unknown Origin Redux

Today we discussed a very complicated (perhaps too complicated) case of a patient with fever of unknown origin, pancytopenia with granulomas in the bone marrow, probable disseminated intravascular coagulation, altered mental status and abnormal liver function.

The consultant, an infectious diseases specialist, went through a very broad differential diagnosis which I will attempt to re-create for you.

Non-infectious:

• Hematologic malignancy
• Non-hematologic malignancy (i.e. renal cell carcinoma)
• Venous thromboembolism
• Inflammatory:
  
  • Vasculitis -- i.e. temporal arteritis
  • Collagen Vascular Disease -- i.e. SLE
    
• Endocrine -- i.e. hyperthyroidism
• Periodic Fever Syndromes
• Factitious fever

Infectious:

• Viral:
  
  • HIV, EBV, CMV, influenza, measles/mumps, other.
• Bacterial:
  
  • Endocarditis, occult abscess, osteomyelitis from various pathogens
  • Unusual bacterial causes (see below)
    
• Fungal:
  
  • Endemic fungi such as:
    
    • Histoplasmosis (Ohio river valley, St. Laurence River Valley, Montreal in 1960s, Caves w/bats)
    • Blastomycosis (Northwestern Ontario)
    • Coccidiomycosis (Southwestern US)
• Mycobacterial
• Parasitic -- i.e. malaria (usually non-falciparum), babesiosis

---

Unusual bacterial causes

Some of these were discussed today:

• Rat-bite fever
• Meilodosis (travel to Australia, Southeast Asia)
• Plague
• Brucellosis (travel, exposure to sheep, cattle, goats, unpasturized cheese)
  
• Bartonella Henselae (Cat Scratch Disease)
• Q-Fever (Sheep, Pregnant Cats, high rates in Nova Scotia)

The key is the travel and exposure history and an open mind.

Day #8 - The Bacteremia that Won't Go Away

Today the discussant described evaluating for exit site and tunnel infections and differentiated these from catheter tip infections with bacteremia. We then talked about diagnosis and management of line-related infections focussing of a few specific pathogens. Here are a few take-away points:

One should obtain paired, labeled blood cultures from the periphery and line in question. The differential time to positivity can help determine whether the line is the source of the infection as follows

• Line and blood simultaneously positive suggests that the line is not the focus
• Line positive 2 hours before periphery suggests that the line is the focus
• Line positive and blood negative may suggest colonization only

In cases of Staphylococcus aureus, Pseudomonas sp., or Candida sp. unless there is some tremendously good reason to keep the line it should be removed.

• Failure to remove the focus/line can be associated with adverse outcomes including metastatic infection and death.
  
• Changing over a wire or reinsertion at the same side is not ideal but sometimes the only solution.
• If the line is not medically necessary and is easy to remove without complication it should probably be removed in most line related infections.
  

Treatment is then dependent on the presence or absence of metastatic infection and should be tailored to the organism and its sensitivities.

• One should be vigilant for evidence of metastatic infection or complications.
  
• Recurrent bacteremias with the same organism are highly suggestive of an occult/endovascular focus.
  

I will also take this moment to point out that for sensitive Staphylococcus aureus treatment with VANCOMYCIN is inferior to a BETA-LACTAM in the non-severly allergic patient.

---

We also talked about two interesting pathogens involved in this case:

• Staphylococcus lugdunensis which is a coagulase-negative staphylococci which has virulence similar to Staphyloccocus aureus and is a cause of endovascular infections such as native-valve infective endocarditis
• Achromobacter xylosoxidans ss xylosoxidans which is a rare gram negative rod which has been known to cause infections such as bacteremia and more rarely pneumonia, abscesses and meningitis. Patients with malignancies seem to be particularly at risk.
  

Brain abscess

The cleverly drawn figure above demonstrates the principle mechanisms by which people develop a brain abscess. The mechanism of acquisition of the brain abscess has direct bearing on the likely organisms. The most common mechanism is by spread from the adjacent sinuses or oral cavity making the most common organisms in the immunocompetent:

• Oral streptococci (viridans group, milleri group)
• Staphylococcus aureus
  
• Oral anaerobes including peptostreptococcus, bacteroides and fusobacterium species

Empiric coverage should, in the absence of a focus outside of contiguous spread, include a third generation cephalosporin at meningitic doses combined with metronidazole.

The "heart" in the diagram includes:

• Hematogenous spread in bacteremia such as seen in the lung/brain or liver/brain axis
• Right to left shunting in HHT or cyanotic heart disease or other AV malformations
• Infective endocarditis
  

A full issue of the journal neurosurgical focus is dedicated to brain abscess. A recent article on using molecular sequencing to identify pathogens in brain absess suggests more pathogens are present in these abscesses than commonly thought -- even though it is unclear how many of them are involved in the actual pathogenesis.

Fever and Polyarthritis

Review article here from NEJM

Consider the following most common etiologies:

1. Infectious:
   
   • Bacterial Infection of Joints
     
     • Staphylococcus aureus
     • Group G Streptococcus
     • Neisseria gonorrrhoeoe and meningiditis
   • Bacterial Endocarditis
   • Lyme disease
   • Secondary Syphilis (usually with rash)
     
   • Mycobacteria/Fungal
   • Viral
     
     • Parvovirus B19
       
     • Rubella
     • HIV seroconversion
     • Hepatitis B and C
2. Post-Infectious
   
   • Reactive arthritis post Chlamydia or enteric infection
   • Rheumatic Fever or Post-Streptococcal Arthritis
3. Rheumatologic
   
   • Rheumatoid Arthritis
   • Lupus
   • Systemic Vasculitis (i.e. PAN)
   • Still's Disease
   • Crystal Induced Arthritis
4. Other (i.e. IBD associated arthritis)
   

We also talked today about the approach to septic arthritis.

Surgery for Infective Endocarditis

Recent publication in circulation addresses the issue very well.

For the cutting edge -- vegetectomy (removal of vegetation) without valve replacement may be an option worthy of study.

See previous posts on IE for more info on IE.