HIV and the brain

Today I facilitated morning report where the presented a case of encephalopathy in a patient with advanced HIV. There was a good possibility this was related to HIV encephalopathy assuming cryptococcal meningitis (prev blog) was ruled out. I have previously blogged about acute confusional states here including links to discussions on paraneoplastic syndromes.

This is a recent review of HIV and its neurologic sequelae. Another review is available here. A more focussed review on HIV encephalopathy including treatment options is available here.

This is a helpful article on the neuroradiology of HIV related CNS processes.

From the Conference: Notable papers in treatment of mucormycosis

As referenced by Dr. Rotstein:

Epidemiology in Transplant patients (link)
Epidemiology in All patients (link)
Clinical trial low vs. high dose AmB (link)
Review of management of mucormycosis (link)
Combination polyene and echinocandin evidence (link)

Not referenced by Dr. Rotstein, but I find it interesting:
Risk of death without initial AmB therapy for invasive mould infections (link)

From the Conference: Hot Topics in HIV

As presented by Sharon Walmsley:

1. "When to start"
   At diagnosis? Treatment as prevention
   
   • Sullivan P et al., 16th CROI Montreal, Feb 2009: 3,000 discordant couples no ARV vs. partner on treatment -- dramatically reduced risk of linked infections 3.4/100 vs. 0.7/100 person years
   CD4 500? 350? 200?
   Viral load - higher?
   Co-morbid illness
   Initiate at dx vs. CD4:
   • Fitzgerald D, et. al, 5th IAS: Cape Town, South Africa July 19-22, Abst. WESY201 stopped due to excess death in delayed arm
   • Kitahata M, et al: Cohort study: individuals who deferred HAART to below CD4 500 were at increased risk of progression.
   • Sterne J et al., 16th CROI Montreal Feb 2009: Cohort study: advantage to starting earlier in terms of risk of AIDS or death regardless of CD4 count
2. "Inflammation is BAD"
   DAD Study:
   
   • Friis-Moller N et al, CROI 2006: Are ARVs associated with increased cardiovascular events? PIs associated with increased risk of CVD above risk of dyslipidemia.
     
     • Baseline MI risk 1.6%, 1.9x more ABC, 1.6 more PI, 3x more smoking
       
     • Associated editorial by Friis-Moller here
       
   • Sabin C et al., CROI 2008; Lundgren JD et al, CROI 2009: Increased risk with ABC, ddI, lopinavir
   • Lang S et al, 16th CROI: ABC exposure within 6 months was associated with slight increase in MI risk, also lopinavir and indinavir
   • GSK and VA study to not find similar ABC risk
     
   SMART Study:
   
   • Do planned structured treatment interruptions benefit patients? No -- there was increased risk of CV death and death from OI
3. Antiretroviral monotherapy - Has it come of age?
   AZT inferior to AZT+3TC inferior to AZT+3TC+PI/NNRTI
   But what about newer single agent:
   
   • LPV/r monotherapy (example publication of this data here):
     
     • Either as initial therapy, with NRTI backbone then stop, with any regimen that supresses then change to monotherapy
   • MONOI Study (Katlama, IAS 2009 Abstract) - Darunavir/ritonavir as monotherapy:
     
     • Suppress then monotherapy vs. continue -- 94% virologic success with DRV/r monotherapy at 48 weeks vs. 99% with DRV/r +NRTIs. Failed to meet pre-specified inferiority
   • MONET Study (J. Arribas et al, IAS, Cape Town July 2009)
     
     • Non-inferiory of monotherapy to with NTRIs -- 84.3% vs. 85.3% @ 48 weeks
4. "Mother to child transmission - has it been eliminated?"
   Risk is currently less than 1% with antenatal testing, antenatal ARV to VL below 50, selective elective C-section, neonatal ART and avoidance of breast feeding
   
   • Does C-section add anything to HAART? Yes, if not on ART or VL not less than 50
   • Treat mother or newborn? Shapiro R, et. al 5th IAS Cape Town/Chasela C. et al, 5th IAS
     
     • If you treat the mothers, get them undetectable, than even with breast feeding transmission can be less than 1% -- of potential great benefit in the developing world
5. "New Drugs"
   
   • Goal is VL less than 50 regardless of naive or experienced with regimens of 2-3 active drugs from different classes
   • Will initial regimens change?
     
   • Entry inhibitors (CCR5 blocker - requires tropism assay) - miraviroc
   • Integrase inhibitor - raltegravir, elvitegravir
   • Maturation inhibitor - bevirimat
   • New agents, old classes: etravirine, rilpilvarine (NNRTI), tipranavir, darunavir (PI)

From the Conference: Hot Papers in ID

As presented by Matthew Muller (in order of presentation):

1. "The Animal Rule" - Raxibacumab for the Treatment of Inhalational Anthrax
2. "The Acid Truth" - Acid suppressive medication use and the risk of hospital-acquired pneumonia
3. "If it ain't Dutch, it ain't much" - Decontamination of the Digestive Tract and Oropharynx in the ICU
4. "Zero Tolerance for CLI" - Chlorhexadine-Impregnated Sponges and Less Frequent Dressing Changes for Prevention of Catheter-Related Infections in Critically ill Adults: a Randomized Controlled Trial
5. "Short Red Snappers" - Adverse Events with 4 months of Rifampin therapy or 9 months of isoniazid therapy for latent TB
6. "Short Red Snappers (2)" - Moxifloxacin vs. Ethambutol in the initial treatment of tuberculosis: a double-blind, randomized, controlled phase II study
7. "Maybe yes, maybe no" - Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. Accompanying editorial here.
   
8. "Pandemic Influenza - Much ado about nothing?" - Severe Respiratory Disease Concurrent with the circulation of H1N1
   

Septic Thrombophlebitis

Not surprisingly, this clinical entity is similar in many ways to both deep vein thrombosis and bacteremia.

Most common sites include: pelvis in association with C-section, IJ in association with infections of head/neck, portal vein related to intrabdominal infections such as diverticulitis or appendicitis, and the veins of the upper limbs in association with indwelling central catheters

Treatment involves medical therapy with intravenous antibiotics and often heparin (review here). Surgical intervention or thrombolysis are reserved for refractory cases. Treatment duration variable.

• In uncomplicated cases, with limited superficial vein involvement, and negative blood cultures, treatment can be as short as 48h past clinical stability, normalization of the white count, and defervessence.
• In other cases with bacteremia and/or metastatic spread treatment duration will range 2-6 weeks.

This article reviews Lemierre's syndrome (also see orignial article from 1936) -- Septic thrombophlebitis of the internal jugular vein with associated Fusobacterium necrophorum septicemia and metastatic infection.

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.

Ventlator Associated Pneumonia (VAP)

Good reviews are available here and here.

Diagnosis:

10-20% of patients receiving mechanical ventilation for more than 48 hours will develop VAP

Some controversy exists about how to precisely define the diagnosis. However in general if you have a new or worsening CXR infiltrate with two or more of:

• Fever or hypothermia
  
• Sputum production
• Increased WBC count

You should be considering VAP. Use of the Clinical Pulmonary Infection Score can be very useful in guiding your approach to the patient with possible VAP.



A score of greater than or equal to 6 is suggestive of VAP. You should obtain samples from the LOWER respiratory tract -- not ET aspirates. There is a study suggesting ET aspirate is acceptable, but patients with Pseudomonas and MRSA were excluded as were many other patients. Samples may be obtained from either direct visualization with BAL or blind BAL, ideally before antibiotics, but antibiotics should not be significantly delayed.

Prevention:

• elevation of the head of the bed
• daily sedation vacations or even awake ventilation
  
• assessment of readiness to extubate
  
  • "if you never re-intubate any patients, you are not extubating soon enough"
    
• peptic ulcer disease prophylaxis
• deep venous thrombosis prophylaxis
• orogastric feeding as opposed to nasogastric
  
  • use of feeds in general is associated with less colonization

Treatment:

• Initiate good empiric therapy based on local hospital epidemiology
  
  • Piperacillin-Tazobactam PLUS ciprofloxacin is suggested @ our site
  • Vancomycin if high suspicion for MRSA
    
    • NB: The vancomycin vs. linezolid debate discussed here
      
• De-escalate approrpiately -- Tailor to cultures, CPIS less than 6 @ 72h consider early discontinuation
• Duration: Treat for 8 days if clinically improved, CPIS less than 6, 15 days if not improved or if Pseudomonas or MRSA (JAMA trial here)

Interesting article on VAT -- a proposed precursor to VAP is available here.

Klebsiella Liver Abscess

See previous liver abscess blog

These articles describe a syndrome of klebsiella liver abscess caused by a so-called hypermucoviscous strain that presents with liver abscess and metastatic complications including CNS infection, endopthalmitis, septic pulmonary emboli, and pericarditis.

Fever in the Retuned Traveller

This was technically yesterday's case -- but since we only had one case today I thought this would be a better topic for the blog.

Two excellent reviews of the spectum of illnesses causing fever in the returned traveller are available from CID here and the NEJM here.

Keys in history:

• What pre-travel preparation (vaccines, prophylaxis) was received? Was it taken? How many doses were missed?
• Where did they go (as exact as possible)? What were the exact dates and places?
• When did they return?
• When did they get sick?
• What exposures did they potentially have?
  
  • Food
  • Water (drinking/swimming)
  • Animals (including humans -- i.e. sexual contacts, blood exposure, sick contacts)
  • Vectors (mosquitos, ticks, other)
• What, if any, localizing features do they have on history or physical exam?

Then, after excluding malaria (from malaria regions) you put the history in context with the duration of illness, and where they went to arrive at a likely diagnosis.

A recent publication using the same database suggests that of the diarrheal illnesses, parasitic infections are most common, followed by campylobacter, shigella and salmonella.

Varicella (Herpes) Zoster Redux

Today we saw a case of multidermitomal shingles with V1 disease and associated VZV keratitis. See previous blog on shingles here.

Additional interesting zoster related articles:

• Recent JAMA clinical cross-roads, including discussion on post-herpetic neuralgia.
• Mayo Clinic Proceedings Review with good table on PHN.
  
• Case reports of disseminated zoster in patients with HIV despite good CD4 counts
• Good review of acute retinal necrosis (ARN) and treatment thereof