Mandatory influenza vaccination?

Article on changing policies in the USA here...

If you don't take the temperature, the patient can't have a fever...

This article reminded me of one of the fatman's rules from Shem's novel.  In this study, computer rule generated central line infection rates were significantly higher than those reported by infection control teams --  in the modern era of reporting and pay for performance, one does wonder if, given a case that is grey one may be more inclined to call it black or white.

Blastomycosis

I saw a case of cutaneous blastomycosis in clinic today -- two lesions, one on the face, the other on the buttock in an otherwise healthy male patient.  A nice review is here.

Blastomycosis is a dimorphic (mould at room temperature, yeast at body temperature) fungus which is endemic in certain geographic areas of North America.  Ontario, where I currently live, and in particular northwest Ontario by the Manitoba border is one such geographic hot spot.

The most common sites of infection are:

• Pulmonary (most patients have some pulmonary involvement)
• Presents as acute (including ARDS) or chronic pneumonia, pulmonary nodule, asymptomatic
• Cutaneous (in 40-80% of cases) presenting as verrucous or ulcerative skin lesions (like my patient)
• Osteomyelitis (~25% of extrapulmonary) presenting as painful lesion in bone, which can mimic sarcoma in radiographic appearance.  Occasionally can have concomittant septic arthritis in adjacent bone.
• GU: (10-30%) in men prostate, testicle, epididymis.
• CNS (5-10%), usually chronic meningitis, occasionally space occupying lesions
• Other

Treatment is with amphotericin B for severe disease (or CNS induction) or with azoles (itraconazole or voriconazole) for other forms.  Treatment guidelines from the IDSA are available here.

New HIV Guidelines

vailable July 21 issue of JAMA (free, please read the full article from there).

Not sure I agree with all recommendations.  This is the curse of 'growing up' in medicine and therefore developing your own opinion.

I think it is too early to consider raltegravir (and maybe even darunavir) as first line therapies in treatment naive patients.  Especially with other options available.  The authors hint at this point but are not explicit enough for the audience of the guideline (in my humble opinion)

Likewise for starting with CD4 greater than 500.  Those patients should be enrolled in properly designed prospective studies (hence the CIII recommendation)

Format revision and Candidemia Line Removal

Since I have left the clinical ID teaching service as a fellow -- hopefully to return as faculty in 2011, I will slightly alter the blog format.  I will highlight interesting cases that I see in my individual practice, and will highlight what I think are interesting/notable articles in the current literature.

This week's post:

Challenging dogma:  Central lines may not need to be removed early in candidemia???

Subgroup analysis of 2 RCTs in treatment of candidemia (mainly echinocandin and lipid ampho B used)
Looked at removal 24-48h vs. later removal vs. retention
842 total, 354 removed early 180 removed late 304 retained

Note that it appears in multivariate analysis that CVC removal was not associated with treatment success or mortality.  But the point estimates are in favor of removal and the CI's are wide.

In the univariate analysis CVC removal within 48h was associated with improved survival.

Why?  Were sicker patients having their lines retained leading to the perception of increased mortality (that was adjusted for in the multivariate analysis). Statistical confounding?

The associated editorial is worth reading.


I also see candidemia reported -- but not other metastatic complications such as endopthamitis, which would be clinically relevant but not noted in surveilance blood cultures.

Bottom line:  An interesting read that challenges dogma, and I think lends itself to further analysis with large enough numbers and robust enough data to exclude a meaningful clinical benefit of earlier removal.

Until then -- please remove my line promptly should I ever have a CVC related candidemia.

We spoke today about Group A Streptococcus (Streptococcus pyogenes).  I thought it would be reasonable to quickly review rheumatic fever (see review).

Diagnosis (Jones Criteria):

MAJOR:
Carditis

• Can affect pericardium, myocardium, endocardium, and epicardium.  Pericardium:  pleuritic chest pain, pericarditis.  Endocardium: usually new mitral regurgitation.  Epicardium:  Conduction abnormalities.  Myocardium:  Can mimic myocarditis.

Polyarthritis

• Knees, elbows, ankles, wrists.  Often overlapping and migratory.

Chorea

• Often unilateral chorea.  Emotional lability.  Weakness.  Sensory change is not seen.

Erythema marginatum

• Evanescent, pink rash with circumsribed borders.  Usually on trunk/arms.

Subcutaneous nodules

• Painless with normal overlying skin on bony surfaces and tendon.  A few mm to 1cm in size. Usually 3-4 and symmetric.

MINOR
Arthralgia
Fever
Elevated CRP
Prolonged PR interval

Diagnosis:  2 major or 1 major 2 minor.  Debate as to how sensitive these criteria are -- and they may lead to undertreatment/diagnosis.

Note:  At time of diagnosis up to 75% will be culture negative.  Usually happens about 2-3 weeks post infection.  The ASOT can be helpful (but isn't perfect and many labs don't do it anymore) particularly if it rises with 2 samples taken 2 weeks apart. 

See previous blog about peripartum sepsis and toxic shock syndrome including treatment thereof.

See necrotizing fasciitis described in this blog including role of IVIG and prophylaxis of close contacts.

Penicillin Allergy

Not to be understated in terms of potential severity, it is true that the number of penicillin 'allergic' patients far outnumbers the number of patients with an actual allergy to penicillin.

The validity of allergies to penicillin recorded in the chart is questionable. The JAMA classic article on history of pencillin allergy is here.

This study (and others) shows meropenem is *likely* safe in patients with IgE mediated penicillin allergy.

The following review article discusses the use of other agents and a strategy for evaluating patients with penicillin allergy. This review discusses antibiotic allergies in general.

***

The ACLS guidelines for the management of anaphalaxis are here.

Delusional Parasitosis

Interesting case today -- and sad. Delusional parasitosis can be very difficult to treat and can be debilitating for patients. There is a role for consult liason psychiatry and newer generation antipsychotics (see review here).

An interesting case report of IATROGENIC delusional parasitosis (i.e. patient believed she had infestation because her doctors told her she did) is here.

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.

PCP with steroids

Frequently invoked, rarely proven the development of PCP with steroid therapy is rare but important to consider.

TMP/SMX prophylaxis for PCP in patients on high dose steroids (Table below) from this meta-analysis. In general, though there is no consensus, PCP prophylaxis should be considered in patients on greater than 30mg of prednisone for greater than three months or those who are on moderate-high dose steroids with another immunosuppressive agent (i.e. patients with Wegner's)

However, the story may be different in lymphoma treatment, particularly with rituximab and high dose CHOP therapy but overall is also low in hematologic (exclude ALL) and solid organ malignancy.

Vancomycin Nephrotoxicity

A review of vancomycin nephrotoxicity is available here.

The IDSA guidelines for therapeutic drug monitoring of vancomycin here.

The first vancomycin trough achieved seems to have predictive value for who will develop nephrotoxicity.

The role of dialysis in acute vancomycin mediated renal injury is discussed here (little evidence from which to draw conclusions, but seems reasonable).

Recurrent HSV Encephalitis

Interesting case. Second episode of Herpes Simplex encephalitis in an adult approximately 3 years after the first. Here is a case report and literature review on recurrent disease.

The main deteminant of outcome in HSV encephalitis is time to acyclovir. This article discusses factors associated with the delay of administration.

This article discusses the outcomes of HSV in population based study.

I discuss viral encephalitis in a previous blog.

Neutropenic Entercolysis

With thanks for the suggestion.

Today we saw a patient with lymphoma, status post bone marrow transplant, who developed fever, neutropenia, abdominal pain, diarrhea and colitis on CT scan with a presumed diagnosis of neutropenic enterocolitis.

This condition, loosely defined (but best defined as fever, abdominal pain and colonic thickening -- see here) is seen in about 5% of patients. The mortality approaches 50% in some studies.

Ultrasound may be useful in screening for this condition early on.

Usual pathogens are bacterial (gram negative bowel flora including pseudomonas, and gram positive bowel flora). Bacteremia is seen in 35-80% of cases. A reasonable coverage choice would be an anti-pseudomonal beta-lactam (i.e. piperacillin-tazobactam or meropenem) with anerobic activity, or something like ceftazadime with metronidazole.

Fungal infection is rare (~5%) and usually candidal, but caries a high mortality (~80% in some studies). Emperic antifungal coverage should be considered if still febrile and neutropenic at 5 days or in the severely ill.

Critically ill patients should be considered for colectomy as should patients with complications (megacolon, perforation).

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'

Strongyloides - The saga continues

We discussed strongyloidiasis at length again today.

See previous blogs on 'strongy' here and a previous blog on eosinophilia here.

Epidural Abscess

We have seen a number of cases of epidural abscess this week. Reviews here (Lancet Neurology), and here (NEJM). Not to be confused with the coolest name in medicine Pott's puffy tumour as described here.

Epidemiology:

• Rare - about 0.2 to 2 per 10,000 admissions
• Often underlying condition:
  
  • Diabetes
  • Alcoholism, Injection Drug Use
  • HIV
  • Chronic spine disease
  • Previous spine surgery
  • Indwelling catheters

Pathogenesis:

• Contiguous spread of infection from soft tissue/vertebrae/manipultion (~30%)
• Hematogenous seeding ~50%
• Unknown 15%
• Can injure spinal cord leading to paralysis due to compression (local) or small septic emboli causing infarction.

Microbiology:

• Most ~60% are Staphylococcus aureus including MRSA
  
• Can be CNST if hardware in situ
• E. coli from bacteremic urinary tract infection
• Pseudomonas (often injection drug use)
• Other: enterococcus, viridans group streptococcus, mycobacteria, fungus (candida, other) etc.

Diagnosis:

History:

• Pain is common, initially localized, then radicular and referred (85%)
  
• Increasing weakness as cord is involved and sensory loss
• Bladder and bowel involvement occur later then fullparalysis
• Fever may be absent! Especially if NSAIDS or acetominophen for pain

Labs:

• Normal WBC in up to 40%!
• Most have elevated CRP and ESR
  
• Bacteremia in up to 60%

Imaging:

• MRI is test of choice.
  
• Concomittant osteomyelitis seen in ~80%. This may be seen on CT; but the abscess can be missed with plain CT.

Treatment:

• If stable and no imminent neurologic comprimise, it is best to get a definitive diagnosis. Blood cultures should be sent and operative specimens. Then antibiotics can be started tailored to the etiologic agent.
• Usually combined medical and surgical management is required. The deficits can progress exceptionally quickly (i.e. complete paralysis within hours) and can be irreversible (particularly if paralysis has been for more than 36 hours!
• If empiric coverage is required, coverage for Staphylococcus aureus, including MRSA as well as gram negatives should be started. Antipseudomonal coverage may be required if there is a risk for pseudomonas -- i.e. IDU, known pseudomonas elsewhere.
  
  • One reasonable approach would be to start VANCOMYCIN (MRSA) and either CEFEPIME, PIPERACILLIN-TAZOBACTAM, or CEFTAZADIME

Common pitfalls - See figure from NEJM below:

Prognosis:

• Paralysis will develop in 4-22%. Paralysis is likely to be irreversible after 24-36 hours
• With prompt surgery most patients have as good or better neurologic status than they did before the OR.
• Death does occur in about 5%
  

MRSA pneumonia

Today we saw a case of severe methicillin resistant staphylococcus aureus (MRSA) pneumonia (review). In the era of community acquired (CA-MRSA), this is becoming a significant problem.

Management includes:

• Supportive care in keeping with best practices
• Vancomycin is the 'gold standard' -- but not a great one.
  
  • aim for trough ~ 20
  • avoid in MIC greater than or equal to 2 (and maybe even 1)
    
  • addition of rifampin improves short term microbiologic cure, but interestingly was associated with increased long term mortality
• Alternatives include:
  
  • Linezolid -- often postulated, not yet proven to be superior.
    
    • the maker of linezolid was fined for off label marketing of the drug for the use in MRSA pneumonia (see one example news article here) so caveat emptor...
  • Tigecycline -- theorhetically 'better' lung kinetics than vancomycin -- not studied
  • Ceftobiprole -- under study. Has advantages in terms of tissue penetration and the fact that it is a beta-lactam
  • doxycycline or TMP/SMX -- could be an option for milder disease.
  • Daptomycin -- do not use, inferior.
• Duration of therapy 8-14 days (or longer in bacteremia with other focus) depending on resolution of clinical symptoms. Some studies show no difference between 8 and 15 days of therapy. Many experts 'prefer' 14 days.
  

Necrotizing Fasciitis

Today we saw a case of necrotizing fasciitis (see previously blogged). This case was in the abdominal wall and perineum of a female patient with obesity and diabetes, and is likely polymicrobial (type I).

While people often use 'Fournier's' gangrene to infer disease in males that involves the scrotum, the disease entity, involving the pereneum does occur in women. In fact, women seem to have higher mortality, possibly because of involvement of the retroperitoneal space due to anatomic differences and also due to delays in diagnosis. This article also suggests that disease in females is underrecognized, and that ano-rectal disease is far more dangerous precipitant than urological disease.

Death and amputation are more likely at extremes of age, with advancing comorbidities (including diabetes), with sepsis, and with visible gangrene on presentation.

CMV Esophagitis

Today we saw a case of a patient with renal transplant who developed CMV esophagitis and also has a newly diagnosed high grade B-cell neoplasm in need of chemotherapy.

This raised a number of questions which I have attempted to answer with the associated references.

1) How do we manage this patient?
2) When can we safely provide cancer treatment?
3) Why did this happen?

The American Journal of Transplantation has a set of guidelines which has recently been updated. The guidelines for CMV prevention and treatment are available here. These guidelines are similar, but in the bone marrow transplant population.

This article looks at risk factors in renal transplantation for developing CMV disease.

This article addresses what happens to patients with pre-existing CMV disease (or recently treated) who go on to SCTx.

Finally, this article describes/summarizes post transplant lymphoproliferative disorder (PTLD) which this patient's lymphoma likely is related to.

Choramnionitis with Beta-Hemolytic Strep Bacteremia

Today we discussed a case of presumed choramnionitis with beta-hemolytic strep bacteremia. I have previously blogged about GBS here and peripartum GAS infection here.

This article, while basic, is a reasonable review of the role on parenteral antibiotics in peripartum women with fever. I would probably choose slightly different antibiotics if giving more than one/two doses. This article discusses the differential diagnosis of peripartum fever.

This cochrane meta-analysis questions the practice of peripartum prophylaxis in known GBS patients... I'm still convinced it is a good idea.