Day #31 - Fever of Unknown Origin

Today we discussed a case of true fever of unknown origin.

Epidemiologic Criteria:

• Fever x 3 weeks (38.3)
• Failure to find cause despite appropriate initial outpatient/inpatient investigations

Causes:

• Majority unknown
• Then infection (most commonly TB or occult abscesses), inflammatory, malignancy, other

Diagnostic tests (beyond initial):

• CT abdomen to look for abscess, lymphadenopathy, other pathology. Yield ~20%
  
• Bone scan (insensitive, but specific with good + LR)
• Liver biopsy -- regardless of hepatomegaly or LFT abnormalities has yield ~15%
• Temporal artery biopsy in the elderly -- yield ~ 15%
• Leg dopplers -- yield 2-6%
• Bone marrow biopsy-- in those with cytopenias or compatable syndromes. Yield ~1%

Meningitis

The meningitis lecture from today is available here.

Day #24 - Colitis

Today we discussed a gay male with fever, abdominal cramping, tenesmus and bloody diarrhea. The discussant made a very important point -- the clinical context and history are very important in making the diagnosis in acute colitis.

Before making the diagnosis of IBD one should exclude infections by history and special tests. Infections can mimic IBD clinically, radiographically, and endoscopically.

I wanted to talk about the differential diagnosis of bloody diarrhea with fever.

Differential Diagnosis

Infectious

• Enteroinvasive infection: Salmonella, Shigella, Campylobacter, E. Coli 0157:H7 (associated with HUS, frequently afebrile), Clostridium difficile, Klebsiella oxytoca
  
• Associated with receptive anal intercourse: HSV proctitis, gonorrhea, chlamydia (L serovar - AKA LGV/lymphogranuloma venerium), syphilis
  
• Associated with oral-anal practices or colonic irrigation: intestinal amebiasis
• More chronic, associated with the terminal illeum: intestinal tuberculosis
• Immunosuppressed patients: CMV colitis
  

Inflammatory

• Ulcerative colitis/Crohn's disease
  

Ischemic Colitis

There is also a good case of a patient with fever and diarrhea in the NEJM available here.

TGH "Case of the Week" July 14-18, 2008

30F with known HIV (CD4 unknown, not on treatment) presents with acute onset fever, chills, rigors, and cough with sputum. On exam she is febrile, tachycardic, hypotensive, hypoxemic on room air requiring hi-flow oxygen to maintain saturations >90% and in moderate respiratory distress.

The chest x-ray is taken and appears below:



Questions:

1) What is the most likely microbiological diagnosis?
2) What is the differential diagnosis?
3) What tests would you order to make your diagnosis?
4) What empiric treatment would you initiate in the ED?

BONUS: What "management strategy" would you employ in the ED and what journal was the study published in?

Thank you to the people who submitted answers. The "contest" is closed for this week. The winner will be notified in person.

"Answers"

1) The most likely etiologic agent to cause a lobar pneumonia in a patient with HIV is still streptococcus pneumoniae. In fact, patients with HIV are at an increased risk of getting pneumococcal infections and should all be vaccinated with the polysaccharide vaccine.

2) The differential diagnosis includes lobar pneumonia with the other organisms of community acquired pneumonia including haemophilus influenzae, moraxella cattharalis, and Staphylococcus aureus. Of particular concern in a patient who is rapidly deteriorating is community acquired MRSA necrotizing pneumonia.

Other causes would include Legionella pneumophillia and if risk factors such as underlying structural lung disease enteric gram negative organisms.

Upper lobe pneumonia should prompt concern for tuberculosis, although in this case the acquity and sepsis-syndrome argue more strongly in favor of bacterial pneumonia.

PCP tends not to be lobar and consolidative and the classic x-ray appearance looks more like bilateral peri-hilar interstitial infiltrates.

Fungal pneumonias like cryptococcal pneumonia, blastomycosis, invasive aspergillosis are unlikely and would not generally have this radiographic appearance and acute presentation.

3) Blood cultures should be sent ASAP (ideally before antibiotics) as they may be positive in up to 25% of cases of pneumococcal pneumonia. Sputum cultures should also be sent for conventional culture, legionella culture and TB culture. I would not recommend sputum for PCP in this case.

Urinary antigen detection for pneumococcal antigen is used in some centres (not here). Urinary antigen testing for legionella can help make this diagnosis.

CD4 testing in acute illness may not be helpful as the acute illness could cause a decrease in the counts; however, it would not be unreasonable as if the CD4 count was >200 rare causes are much more unlikely.

4) In a septic patient with community acquired pneumonia you need to cover broadly for the most likely pathogens. There are many ways to do this and in some cases what you choose will depend on recent antibiotic exposure.

In this case a combination of VANCOMYCIN 1gIV q12h and LEVOFLOXACIN 750mg IV/PO q24h would be appropriate. This would cover MRSA and quinolone resistant pneumococcus, the usual pathogens including the majority of pneumococcus, unusual pathogens like legionella, and many enteric gram negatives.

BONUS: The management strategy to be employed is "Early Goal Directed Therapy in Sepsis"

Day #18 - Cirrhosis

Today's case was of a 52 year-old man who presented with new diagnoses of cirrhosis with ascites, portal hypertension and probable variceal bleed who also had a new diagnosis of diabetes mellitus. The discussant showed us, although in his own uniquely tangential way, the type of clinical reasoning that great physicians use in arriving at a diagnosis.

There are a number of valuable teaching points today:

1) Ascites:

Etiology

• Elevated Hydrostatic Pressure --> CHF, constrictive pericarditis, Budd-Chiari, cirrhosis, IVC occlusion
• Decreased oncotic pressure --> malnutrition, nephrotic syndrome, protein losing enteropathy, cirrhosis/liver failure
• Increased fluid production in peritoneum --> infection (TB), neoplasm

Diagnosis on History/Exam
History

• Increased abdominal girth and ankle swelling are the most sensitive (greater than 85%)
• Past history of hepatitis or cancer are the most specific (greater than 85%)

Exam

• Not likely if no bulging flanks, no flank dullness and no shifting dullness
  
• Likely if fluid wave, shifting dullness, and peripheral edema (LR+3.8/-0.2)

2) Special Tests:

The team today also mentioned that they had performed a paracentesis in order to evaluate the ascites. This is important as paracentesis can:

1. Provide diagnostic clues
2. Exclude SBP

The Serum Albumin-Ascites Gradient (SAAG) is a valuable tool in deciding if the ascites is due to portal hypertension. SAAG = Serum albumin - Ascites Albumin. If <11 style="font-style: italic;">It should also be prevented in cirrhotic patients post GI bleed using TMP/SMX 1DS PO BID x 7d or CIPROFLOXACIN 500mg PO BID x 7d

The diagnosis can be made on the paracentesis:

• PMN >250 (LR + 6 LR - 0.2)
• WBC >1000 (LR + 9)
• Inoculation of blood culture bottles (fill them with required volume) can improve yield of the C/S

NB: In most cases, you do not need to use FFP/Platelets pre paracentesis.

Initial treatment is with CEFTRIAXONE 2g IV q24h with coverage narrowed to the culture data. You need only treat for 5 days.

Patients should get 1.5g/kg of 25% albumin within 6h then 1g/kg on day 3.

NB: Think of missed perforation if multiple organisms grow in the culture or if the WBC count in the fluid is much greater than 1000.

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.
  

Decision making in Community Acquired Pneumonia

Read a great article published in CID on Aug 1, 2008. SMART-COP predicts people with CAP who will require admission to intensive care requiring ventillatory or vasopressor support. It does so better than the PORT score or CURB-65 which really only predict death.

Day #4 - Acute Monoarthritis

Today the discussant spoke about the approach to acute monoarthritis. It was a very articulate presentation and your participation was excellent.

To clarify the point on treatment:

• CEFTRIAXONE 2g IV q24h will cover most organisms including GC, most streptococci, Staph. aureus and many gram negatives. It is not the ideal agent for Staph. aureus, so if it turns out to be methicillin *sensitive* staph. aureus you should change to ANCEF (1g IV q8) or CLOXAILLIN (2g IV q6)
  
• Is MRSA a possibility or is this a prosthetic joint? --> ADD VANCOMYCIN (renal dose)
• Is there reason to worry about pseudomonas? --> I would suggest VANCO+CEFTAZADIME and ID consult.
  

• Prosthetic Joint = Call ortho. Probably should not be admitted to medicine if septic prosthetic joint is the main reason they are in hospital -- they need to go to the OR for wash-out and, in my experience, this is much less likely if they are admitted to GIM instead of orthopedics. Should get ID consult as well.
  

This article from JAMA is an excellent reference on making an evidence based diagnosis of septic arthritis on history, physical and laboratory examination.

VIDEO: How to do an arthrocentesis of the knee

Highlights include:

Risk Factors: Age, DM, rheumatoid arthritis, joint surgery, hip/knee prosthesis, HIV infection, skin infection, (unprotected sexual intercourse for GC)

History: Pain and swelling are present >80% of the time; fever is present only 60% rigors and chills less than that.

Synovial Fluid Exam (LR less than 0.1 rules out; LR >10 rules it in)

• WBC <=25,000 unlikely septic arthritis (LR 0.32) unless immunosuppressed
• WBC >=25,000 LR 2.9
• WBC >=50,000 LR 7.7
• WBC >100,000 LR 28

• PMNs <90%>
• PMNs >90% LR 3.4
  

Important to note that measurement of glucose, protein, lactate do not appear to be helpful according to the literature. Also note that LDH in the joint may have some utility in ruling out as LDH <250>