June 17, 2014 Grand Rounds

Case 1: 73 year old man with neutropenia secondary to chemotherapy for a recent diagnosis of AML who presents with acute onset appearance of diffuse skin nodules and fever secondary to Fusarium sp.

1. Always think of disseminated Candida and Fusarium infection in a neutropenic patient who presents with sudden onset skin nodules and fever.

2. We usually treat serious Fusarium infection with amphotericin plus voriconazole. This is because different species of Fusarium may display different susceptibility patterns. For example. Fusarium solani and Fusarium verticilliodes are azole-resistant while Fusarium oxysporum and Fusarium moniliforme are usually susceptible to either voriconazole or posaconazole.A good review of Fusarium infection in immunocompromised patients can be found here.

3. The greatest risk factor for mortality secondary to Fusarium infection is persistent neutropenia.

Case 2: 7 month old infant who presented with fever, morbiliform rash, acute mental status change, and seizure secondary to vanishing white matter disease.

1. The discussion centered on why measles was unlikely in this case (i.e. vaccination was up to date, measles Ig M was negative, rash preceding onset of fever).

2. The discussion also talked about measles encephalitis. It commonly develops during the viral exanthem or within 8 days of illness onset. Around 51% of patients with measles may have EEG abnormalities in the absence of actual encephalitis. Patients with measles may also have a CSF with <10 cells (15%).

3. Vanishing white matter disease, caused by specific genetic abnormalities, is characterized by gradual disappearance of the white matter after an initial normal development.

Case 3: 49 year old man with diffuse lymphadenopathy, hepatosplenomegaly, fever, constitutional symptoms, and necrotizing granulmatous lesions on bone marrow biopsy

1. Differential diagnoses are broad: tuberculosis, fungal infection, Q fever, bartonellosis, syphilis, lymphoma, et al. A good review is found here.

2. In this patient, multiple cultures failed to isolate an infective agent. Biopsy smears were also negative. In this situation, further tissue biopsy should be done as lymphoma can sometimes be difficult to diagnose.

3. Necrotizing granulamotous disease in a sick patient may warrant empiric anti-tuberculosis treatment while waiting for culture results.

June 10, 2014 Grand Rounds

Case 1: Malaria in a 24-year old returned traveler from Africa and Saudi Arabia

1. Important differential diagnoses in a returned traveler who presents with fever include: malaria, dengue, typhoid fever, rickettsial infection, leptospirosis, and N. meningitidis.

2. Since the patient here presented with fever and prominent headache, African trypanosomiasis (African sleeping sickness) was also included in the differential diagnoses. It was pointed, however, that this diagnosis is very rare. In a cohort of more than 17,000 patients from the GeoSentinel data, only one had African trypanosomiasis. This article can be found here.

3. Coartem (artemether/lumefantrine) is the oral agent of choice for uncomplicated malaria. Malarone (atovaquone/proguanil) is an alternative oral agent. In this patient, Malarone, which was the initial drug administered, did not clear the parasetemia even after 4-5 days of treatment. Parasetemia eventually cleared after switching the medication to Coartem.

4. How soon should we expect clearance of parasetemia with the use of Malarone? In a single study, the use of Malarone led to complete clearance of the parasetemia in all patients on day 3 of treatment. 

5. Atovaquone resistance is easily inducible in vitro. We don't see it a lot in clinical practice because mutations that lead to atovaquone resistance render the parasite less fit.


Case 2: Mycoplasma infection associated with multiple deep vein thromboses and pulmonary embolism in a 14-year old immunocompetent person

1. Remember that Mycoplasma infection can induce a procoagulant state (elevated cardiolipin), much like infection with parvovirus B19, tuberculosis, EBV, CMV, etc.). More 23 case reports have been published in the literature.


Case 3: Extensive cutaneous Alternaria infection in a patient with multiple episodes of bloodstream infections

1. Repeated episodes of bloodstream infection, in the absence of endocarditis, gastrointestinal pathology, central lines, or prosthetic devices should behoove clinicians to do a thorough dermatologic examination. This patient presented with extensive cutaneous Alternaria infection that caused him to develop burn-like lesions enough to compromise cutaneous barrier against infection.

2. The treatment of choice for Alternaria is amphotericin. Posaconazole and voriconazole also display good activity. Surprisingly, some Alternaria sp. have low MIC's to the echinochandins.

June 3, 2014 Grand Rounds

Case 1: Invasive Aspergillus sphenoid sinusitis associated with cavernous sinus thrombosis in a patient with lymphoma receiving chemotherapy

1. The discussion centered on the use of combination antifungal therapy for invasive mold infection. The bottom-line is that, although there is no good data to support the routine use of combination antifungal therapy, no antagonism in vivo and in vitro is seen between different antifungal combinations, especially with that of amphotericin plus an echinocandin. A good review is found here.


Case 2: Acute generalized exanthematous pustulosis (AGEP) secondary to a brown recluse spider bite in a 5-year old immunocompetent child

1. Always keep brown recluse spider bite in your differential diagnosis for somebody who presents with a localized cellulitis that is associated with fever and Coombs-positive hemolytic anemia. The bite of the brown recluse spider does not always have to be obvious. It may sometimes appear as a localized swelling without an eschar. Severe cases can also lead to multi-organ failure and DIC (systemic loxoscelism). A good review is found here.


2. AGEP should always be entertained in the differential diagnosis of diffuse pustular rash associated with fever. The most common cause is exposure to certain medications. Rarely, it can be caused by spider bites. Certain viral infections have also been shown to cause AGEP, including adenovirus, parvovirus B19, enterovirus, hepatitis B, hepatitis C, EBV, and CMV. AGEP can mimic other serious dermatologic conditions including pustular psoriasis of von Zumbusch, Behcet's disease, DRESS, and SJS/TEN. A good review is found here.


Case 3: Scedosporium pulmonary infection in a neutropenic patient

1. All Scedosporium sp. are universally resistant to amphotericin. The drug of choice is voriconazole.

2. Scedosporium prolificans is a nasty fungus. It is known to be resistant to almost all antifungals. Treatment success has been reported with the use of voriconazole plus terbinafine.

3. A "buzzword" for Scedosporium infection among immunocompetent hosts is "near-drowing" since several infections with this fungus have been documented among patients with near-drowning experience.

January 14, 2013 Grand Rounds

Case 1: Chronic cavitary pneumonia  secondary to Pseudomonas aeruginosa

1. This case is particularly interesting as Pseudomonas aeruginosa usually presents as acute pneumonia. Acute necrotizing pneumonia with cavitary formation is a well-recognized complication of Pseudomonas pneumonia. But chronic and progressive cavitary pneumonia secondary to Pseudomonas aeruginosa is probably rare. Although, chronic Pseudomonas airway infection is common among cystic fibrosis patients.

2. Burkholderia pseudomallei, the causative agent of meliodosis, was brought up as a differential diagnosis since the patient is a veteran. Like Mycobacterium tuberculosis, it can lie dormant and reactivate ("Vietnamese time bomb"). As much as 12% of infected patients present with tuberucolosis-like illness, many of whom have cavitary lesions in the upper lobes of the lungs.

Case 2: Necrotizing fasciitis secondary to Klebsiella pneumoniae

1. There are 2 main types of necrotizing fasciitis (NF).

• Type 1 NF: caused by mixed aerobic/anaerobic bacteria; there is usually an obvious portal of entry; you can see gas on radiographic imaging; hard to distinguish from gas gangrene secondary to Clostridium perfringens and Clostridium septicum.
• Type 2 NF: caused by group A Streptococcus, other beta-hemolytic Streptococcus and Staphylococcus aureus; usually no obvious portal of entry; rare to see gas on radiographic imaging.

2. In the western hemisphere, Klebsiella is the 3rd most common causative agent of NF, at least in 1 case series. In Asian countries, on the other hand, it usually is the most common cause, again at least in 1 case series. This may not be so surprising as the hypermucovisous strain of Klebsiella (its most aggressive phenotype) is also more common in Asian countries. The latter is known to cause severe disease including bacteremia, liver abscess, and meningitis.

Case 3: Primary cutaneous aspergillosis

1. Majority of cutaneous aspergillosis represent dissemination from distant foci of infection. A rare disease, primary cutaneous aspergillosis usually results from local trauma to the skin (e.g. intravenous catheter, burn) in immunosuppressed patients.

2. Primary cutaneous aspergillosis is associated with less signs of systemic toxicity compared with primary cutaneous zygomycosis.

3. Voriconazole +/- surgical debridement is the treatment of choice.

January 7, 2014

Case 1: Histoplasma-associated mediastinal granuloma

1. Infection with Histoplasma can lead to 3 different types of mediastinal involvement: mediastinal lymph nodes, mediastinal granuloma, and fibrosing mediastinitis. This is not a disease spectrum since studies have shown that one does not necessarily lead to the other. 

2. Mediastinal lymph node involvement refers usually to the presence of calcified lymph nodes associated with past infection. 

3. Mediastinal granuloma refers to a more serious condition where active granuloma formation leads to compression of  adjacent structures and sinus tract formation in some cases. 

4. Fibrosing mediastinitis is the most feared complication. For some unknown reason, it usually affects younger females. Its occurrence is most likely predicted not by the burden of Histoplasma infection but by the host's immune response to the fungus. Mediastinal biopsy often reveals only the presence of collagen fibers in contrast to mediastinal granuloma where active caseating granulomas are seen on histopathology.

5. No treatment is recommended for mediastinal lymph nodes or fibrosing mediastinitis. Treatment with itraconazole with or without corticosteroids is considered especially for symptomatic persons with mediastinal granuloma.

Case 2: Refractory and recurrent Pseudomonas bacteremia in an immunocompromised patient (a mortality-morbidity discussion)

1. This highlights the difficulty in managing patients with multidrug resistant Pseudomonas infection.

2.In this case presentation, colistin monotherapy was suggested to be more efficacious compared to aminoglycoside monotherapy in patients with Pseudomonas infection. Please refer to the following studies:

• Leibovici et al. PMID: 9145881. Kuikka et la. PMID: 9865983. Both showed increased mortality with use of aminoglycoside monotherapy against Psudomonas bacteremia.
• Petrosillo, et al. PMID:18844682. Presents data on colistin monotherapy against MDR gram negative organisms including Pseudomonas.

Case 3. A case of severe 2009 H1N1 influenza infection requiring intravenous zanamivir 

1. Intravenous zanamivir is used in patients with either suspected neuraminadase inhibitor resistant strain of influenza or in patients with a perceived impairment in gut absorption of oral oseltamivir.

2. Intravenous zanamivir is generally safe and well-tolerated in phase II studies. Increased AST and ALT may be a concern for some patients receiving this investigation drug.