September 16, 2014 Grand Rounds

Case # 1. A 54/M with chronic malaise, low back pain and new-onset heart failure secondary to subacute infected endocarditis (IE) secondary to Abiotrophia defectiva.

Taken from: http://medicine.creighton.edu/medschool/WebAtlas/secure/id/strep1/images/Strep%20NDS.jpg

1. Abiotrophia defectiva and Granulicatella sp are nutritionally-variant Streptococcus (NVS) that require pyridoxal for growth on culture. They are part of the normal oral, gastrointestinal, upper respiratory and urogenital flora. They are known to cause IE but they can also lead to primary bacteremia in patients with hematologic malignancy.

2. Compared with IE caused by viridans group Streptococcus, IE associated with NVS is usually characterized by smaller vegetation but with greater incidence of septic embolization. It also carries higher failure, relapse, and mortality rates. 

3. IE associated with NVS is treated with ampicillin and gentamicin (or vancomycin plus gentamicin for penicillin-allergic patients) similar to Enterococcus-associated IE. 

4. Abiotrophia defectiva shows in vitro susceptibility to vancomycin, rifampin, clindamycin, chloramphenicol, erythromycin, and levofloxacin. On the other hand, Granulicatella sp. are more likely to be resistant to penicillin and cephalosporins compared with Abiotrophia.

Case # 2. An 18/M with h/o bilateral lung transplantation for idiopathic bronchiolitis obliterans 2 years ago and poorly adherent to prednisone, tacrolimus, mycophenolate, and atovaquone presented with acute and progressive respiratory failure secondary to acute rejection; respiratory multiplex PCR tested positive for rhinovirus/enterovirus.

1. From last week's discussion, we know that the detection of rhinovirus/enterovirus using the multiplex PCR test is a clue to the presence of enterovirus D68. Because the patient had respiratory failure, further sequencing was done on the isolate. The isolate was identified as human rhinovirus 36.

2. Rhinovirus, unlike enterovirus, is tropic to the upper and not the lower respiratory tract. However, rarely, it can cause lower respiratory tract disease. Infection with rhinovirus is not associated with acute lung rejection in one case series.

Case # 3. A 30 year old man with well controlled HIV infection on HAART presented with acute rash that involved his bilateral palms and soles as well as acute Bell's palsy. 

Taken from: http://upload.wikimedia.org/wikipedia/commons/2/29/Treponema_pallidum.jpg

1. Bell's palsy occurs in secondary and tertiary forms of syphilis hence, performing a lumbar puncture to rule out neurosyphilis is warranted.

2. This patient had a normal head CT scan and lumbar puncture revealed 0 white cells and normal total protein. The absence of white cells in the CSF can rule out neurosyphilis but a more definitive test (although not standardized) that rules this out is a negative CSF FTA. The latter is usually ordered when the clinical suspicion for neurosyphilis remains in the presence of mild CSF pleocytosis and a negative CSF VDRL.

3. Read more about other unusual manifestations of secondary syphilis (i.e. gastropathy, hepatitis, Bell's palsy, aseptic meningitis ) here.

September 9, 2014 Grand Rounds

Case #1. A 70 year old man with relapsed AML undergoing chemotherapy admitted with fever, fatigue, sore throat, and cough; CT scan showed tracheal enhancement and mediastinitis; bronchoscopy showed pseudomembranous lesions; a case of invasive trancheobronchial aspergillosis

 Taken from: http://www.aspergillus.org.uk/secure/image_library/tracheobronch/fig7.jpg

1. Remember the different manifestations of aspergillosis in immunocompromised patients: pulmonary (from acute nodular lung disease to the more indolent necrotizing/cavitary form), tracheobronchitis, disseminated form, and rhinosinusitis. Less common manifestations that are well described in the literature include central nervous system involvement (brain abscess), endophthalmitis, endocarditis, gastrointestinal, or cutaneous lesions.

2. Invasive tracheobronchial aspergillosis (ITBA) is seen in <10% of patients with invasive aspergillosis. It is usually diagnosed late  because it can have normal imaging early in its course. A predisposed patient who comes in with fever, significant cough, and shortness of breath without pneumonia on chest CT scan should alert you to this diagnosis. Bronchoscopy is the best way to look for it.

3. ITBA has 3 forms: ulcerative (seen in AIDS and heart-lung transplant patients), pseudomembranous (seen in patients with hematologic malignancies), and obstructive (mucus plugs are usually seen but no bronchial inflammation is evident). Mixed forms can also be observed in <10% of patients with ITBA.

4.    ITBA is usually associated with a negative blood galactomannan.

Case # 2. A 15 year old girl presented with acute onset back pain and fever secondary to Group A Streptococcus epidural abscess

 http://images.ddccdn.com/images/pills/mtm/Clindamycin%20300%20mg-RAN.jpg

1. Always keep epidural abscess in your differential diagnosis for fever and back pain especially if patients have neurologic deficits. Be aware of the different stages of epidural abscess symptomatology: stage I (back pain, fever, tenderness), stage II (spinal root signs such as radicular pain), stage III (sensory and motor deficits, bladder/bowel dysfunction), and stage IV (paralysis).

2. This patient was treated with both ceftriaxone and clindamycin initially. The basis of combining clindamycin with penicillin in the treatment of Streptococcus pyogenes infection (especially in cases of high burden infection) early in its course is not only to prevent toxin release (in cases of necrotizing fasciitis) but also to counteract the theoretical Eagle effect. The latter is the paradoxical reduction of the bactericidal activity of high dose penicillin in infections with heavy Streptococcus pyogenes burden. The proposed mechanism is the reduced expression of penicillin-binding proteins by bacteria induced to a stationary phase of growth by the heavy bacterial burden. Clindamycin kills these bacteria in the stationary phase as its ability to inhibit bacterial protein synthesis is not dependent on bacterial growth stage or bacterial load.

Case # 3. Update on enterovirus D68

1. Enterovirus D68 was first isolated in 1962 in California. Since then, sporadic outbreaks have been seen. From 2008-2010, outbreaks have been documented in the Netherlands, Japan, China, and the Philippines. It has rarely been reported in the US until last month (read here).

2. Enterovirus D68 manifests almost exclusively as a respiratory illness of varying severity (from mild illness to frank respiratory failure requiring ventilatory support or extacorporeal membrane oxygenation). Rare cases have been associated with neurologic manifestations (e.g. flaccid paralysis and meningoencephalitis).

3. The clinician should be alerted of this entity when a multiplex PCR give out a result "enterovirus/rhinovirus". The virology lab can be called for genotypic identification as this is the only way to diagnose enterovirus D68. 

4. There are no specific treatments available for enterovirus D68 infection.

September 2, 2014 Grand Rounds

Case # 1 A 47 year old immunocompetent man with no significant past medical history who presented with  6 weeks of headache, neck pain, and fever secondary to Cryptococcus neoformans infection

1. In immunocompetent patients, Cryptococcus neoformans usually affects the central nervous system causing subacute to chronic meningitis. Patients often present with headache that is repeatedly misdiagnosed as migraine or cluster headache. 

2. Apart from HIV infection and receipt of immunocompromising medications (for transplantation, cancer, or rheumatologic disorders), other well-characterized immunodeficiency states that predispose to cryptococcal infection include CD4 lymphopenia and presence of anti-GM-CSF autoantibodies (read here).

3. Further ID pearls about cryptococcal infection are listed under Case # 1 June 24, 2014.

Case # 2. A 7-day old baby girl who presented with increased sleepiness, poor feeding, thrombocytopenia, and a diffuse macular rash secondary to parvovirus B19 infection

1. Parvovirus B19 causes fifth disease (erythema infectiosum). Another well-characterized but rarer and hence, less recognized illness that is associated with a rash secondary to parvovirus B19 is called papular-purpuric gloves and socks syndrome (PPGSS). PPGSS (see picture) is characterized by symmetrical and well-demarcated erythematous lesions on the hands and feet that end abruptly at the level of the wrist and ankle. It can present with high fever, mucosal lesions, and arthralgia (read here).

2. Other well-known illnesses associated with parvovirus B19 include: symmetric arthritis/arthralgia, transient aplastic crisis, chronic pure red cell aplasia, and non-immune hydrops fetalis. Rare manifestations include: acute hepatitis, fulminant liver failure, immune-complex glomerulonephritis, myocarditis, ITP, and TTP.

Case # 3. A 30 year old woman who is 13 weeks pregnant and who has a h/o splenectomy secondary to hereditary spherocytosis presented with fever and acute-onset watery diarrhea 2 days after eating in a restaurant secondary to Campylobacter jejuni infection (blood and stool culture positive)

1. Campylobacter usually causes a self-limited gastroenteritis and hence, treatment is not usually advised. However, treatment is recommended for those who present with severe disease (i.e. bloody diarrhea, high fever, extraintestinal infection, worsening or relapsing symptoms, or symptoms > 1 week duration) or those at risk for severe disease (e.g. immunocompromised, elderly, and pregnant patients).

2. The prevalence of fluoroquinolone-resistant Campylobacter is rising. In Thailand and Spain, for example, the prevalence is as high as 80%. In the US, fluoroquinolone-resistant Campylobacter has also risen from 0% to 19% between 1989 and 2001. Hence, some authorities advocate a macrolide (azithromycin or erythromycin) as first line agent against this infection.

3. Other antibiotics that can be used against Campylobacter include: aminoglycosides, carbapenem (especially for severely ill patients), clindamycin, tetracyclines, and chloramphenicol. It is inherently resistant to trimethoprim and some beta-lactam antibiotics including penicillin and most cephalosporins.

4. Campylobacter fetus is an uncommon species of Campylobacter that usually affects immunocompromised hosts, including elderly and pregnant women, and causes bacteremia and meningitis.

5. More ID pearls about Campylobacter are listed under Case # 2 July 2, 2014.