Infectious Disease

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7/26 VA MTC: Legionella in the water, Antigens in the Urine

Today our residents reviewed a case of an elderly gentleman presenting after 1 week of symptoms that includes fevers, chills, SOB, malaise, nausea, vomiting, and diarrhea. He reported recent travel to Las Vegas and stayed at a hotel with his wife and other friends. Then ~8 days ago his wife started to have symptoms and the next day his symptoms started.

Patient was found to be febrile, hypoxic, and tachycardic on admission. Labs showed a hyponatremia, AGMA, a significant AKI, leukocytosis, and elevated LFTs. We then reviewed the CXR and discussed a differential for our patient’s presentation. Based on the clinical presentation we discussed additional labs/studies to order. These included ESR, CRP, COVID PCR, RPNA panel, hepatitis panel, Legionella Urine Antigen, and Cocci serologies.

Patient was found to have a positive Legionella urine antigen, confirming diagnosis of Legionnaires disease. We then discussed clinical factors that should raise clinical suspicion for Legionella and patient risk factors associated with infections. We reviewed IDSA recommendations for testing all patients with moderate or severe pneumonia given potential severity of symptoms if not treated early. Lastly we discussed different ways to test for legionella, noting that Urine Antigen is the fasted and most common, BUT it only tests for one serogroup of 1 species. Given that serogroup is responsible for >80% of cases worldwide it is still a good initial test, but it does not rule out Legionella if clinical suspicion is still high!

Key Points:

  • Clinical factors that raise suspicion for Legionella- GI symptoms, hyponatremia, elevated LFTs, CRP levels >100 mg/L
  • Recommended to test for legionella in all patients with moderate or severe CAP (hospitalized)
  • Test with PCR or Urine Antigen (remember urine antigen only tests for L. pneumophilia serogroup 1)
  • Cases of Legionella have been increasing steadily over the past two decades
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MTC 7/26: Don’t let your fear of syphilis management “spiro” out of control

Syphilis testing and management can be a confusing topic! That’s why we were lucky to have been joined by ID specialist extraordinaire, Dr. Amutha Rajagopal, this morning when we discussed a case of ocular and neurosyphilis. We reviewed the case of a middle-aged man who presented with subacute monocular vision loss and was found to have posterior placoid retinopathy consistent with ocular syphilis. CSF studies showed a lymphocyte-predominant pleocytosis and an elevated protein level. CSF VDRL was also reactive. He was treated with IV aqueous crystalline penicillin for 14 days.

Diagnosis: While darkfield microscopy is still the gold standard, it is rarely done in practice. Instead, a presumptive diagnosis can be made with a positive treponemal test AND a positive nontreponemal test. Treponemal tests (e.g., CIA/EIA, FTA-ABS, TP-PA) detect antibody response to Treponema pallidum and are nearly 100% specific; they are qualitative and usually remain positive for life after an infection. Nontreponemal tests (e.g., RPR, VDRL) detect antibody response to cellular fragments (e.g., cardiolipin) released as a result of cell damage from syphilis, so false positives are not uncommon. Nontreponemal tests are qualitative and can be used to track disease activity and treatment response. Due to the prevalence of HIV coinfection, don’t forget to test for HIV!

Here at UCSD, we use the “reverse algorithm”: we screen using a treponemal test (chemiluminescence assay), and positive tests are reflexed to a nontreponemal test (RPR). Discordant results (i.e., reactive CIA and nonreactive RPR) requires adjudication with a different treponemal test (e.g., TP-PA). Using the results of these tests and a thorough history and exam (see below), the patient’s infection status can be ascertained.

Treatment: Treatment of syphilis depends on the stage. Primary, secondary, and early latent syphilis (i.e., infection generally acquired in the past year) are treated with a single dose of IM benzathine penicillin G 2.4 million units. Late latent and tertiary syphilis (i.e., infection acquired >1 year ago or duration of infection unknown) are treated with 3 weekly doses of IM benzathine penicillin G 2.4 million units. Neurosyphilis, ocular syphilis, and otosyphilis can occur at any time and are treated with IV aqueous crystalline penicillin G 3-4 million units every 4 hours for 10-14 days.

Remember: CSF VDRL is poorly sensitive (as low as 27%), so a negative test does not exclude neurosyphilis! If the clinical syndrome and CSF studies are otherwise compatible with neurosyphilis, treat with IV penicillin!

Key Learning Points:

  1. To diagnose syphilis, treponemal and nontreponemal tests must both be reactive.
  2. Neurosyphilis can occur at any time and is treated with IV penicillin for 10-14 days.
  3. A negative CSF VDRL does NOT rule out neurosyphilis. Use the patient’s clinical syndrome and the results of other CSF studies to guide you.
  4. HIV coinfection is common in individuals diagnosed with syphilis.

Helpful Link: 2021 STI Treatment Guidelines (CDC, released 7/23/21)

Thank you so much to Dr. Rajagopal for being part of this awesome morning report!

Medical Spanish Word of the Day: la sífilis = syphilis

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    Dr. Annie Cowell–Our Newest Associate Program Director

    Dear UCSD IM Residency Family,

    Please join me in congratulating Dr. Annie Cowell! Dr. Cowell has been appointed as an Associate Program Director for our residency training program.

    Dr. Cowell received her undergraduate degree in Health Promotion and Disease Prevention at University of Southern California, and her medical degree and Masters of Public Health in International Health from Tulane University in New Orleans, LA. She completed residency training in Internal Medicine and Pediatrics at Yale-New Haven Hospital followed by fellowship in adult Infectious Diseases at UC San Diego. She is currently an Assistant Clinical Professor in the Division of Infectious Diseases and Global Public Health.  

    Dr. Cowell is committed to the education of medical students, residents, and fellows and remains passionate about infectious diseases and global health. She is both the founder and Director of the Global Health Pathway and serves as Core Faculty for the ID fellowship program.  She participates in research on malaria with our partners in Mozambique and looks forward to building additional international educational partnerships across the border and around the world.  She is excited to work with everyone more in this new role.

    Please also join me in thanking Dr. Charlie Goldberg for his service to the residency program! Dr. Goldberg served as an Associate Program Director since 2014.  Dr. Goldberg built our Point of Care Ultrasound Curriculum and the BEAM (mini-MBA), as well as our Medical Mystery (patients with physical exam findings) and microaggressions curriculum.  Dr. Goldberg has ascended to the position of Associate Dean of Graduate Medical Education for UCSD and will continue in the role of Core Faculty in the UCSD Internal Medicine Program.

    THANK YOU Drs. Cowell and Goldberg!  We are so fortunate to have such amazing faculty support for our program!!!!

    Sincerely,

    simerjot 

    Annie Cowell, MD, MPH
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    VA MTC 6/17: EBV or not EBV, Mononucleosis

    At today’s VA MTC residents walked through a case of infectious mononucleosis.

    The Case: A young female presented with fever, abdominal pain, and nausea. Additional symptoms included fatigue, sore throat, cough, night sweats, and headaches. After physical exam was reviewed, teams were asked to select only 3 lab tests to order and all were able to come to the diagnosis of infectious mononucleosis.

    We reviewed common lab findings in infectious mononucleosis: lymphocytosis, atypical lymphocytosis, abnormal LFTs, and positive heterophile antibody testing (monospot). We looked at a peripheral smear with atypical lymphocytes. Discussed that if monospot is negative, patient may have early EBV infection in which case you may consider ordering EBV-specific antibody testing or patient may have an infection that mimics mononucleosis including primary HIV infection, CMV infection, or Toxoplasma gondii. We also reviewed counseling patients on risk of splenic rupture and possibility of prolonged fatigue.

    Our awesome expert discussant Dr. Stephen Rawlings taught us about presentations of prevalence of EBV and CMV, splenic rupture, and the mechanism behind the monospot test (Hint: B-cells infected with EBV produce multiple, random antibodies some of which react to the horse or sheep blood in the test).

    Medical Spanish Word of the Day: escalofríos = chills

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    6/16 Noon Conference: Pulmonary infections in immune compromised patients

    Today at our final noon conference for the ID/Global Health block, we had Dr. Kevan Akrami, a PCCM and ID-trained alumni of our residency program join us from Brazil to discuss pulmonary infections in immunocompromised hosts. He led our ward teams through three patient cases that highlighted the immune defects present in various immunocompromising conditions, including fungal and atypical infections. Some overarching themes include: 

    • Host immunity defect, vaccination and prohylaxis history will determine which organisms are most likely to cause infection  
    • Chest radiograph may be atypical or falsely negative with high degree of immune suppression. CT chest increases sensitivity and specificity although limitations remain.  
    • Early diagnosis and treatment are key to decrease morbidity and mortality  
    • Concurrent pulmonary infections can occur in the severely immune compromised  
    • Reconstitution of the immune system can unmask TB or paradoxically worsen (IRIS) on treatment  

    You can find Dr. Akrami’s slides on our blog here.

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    5/26 Noon Conference: Multi Drug Resistant Tuberculosis with Dr. Laniado-Laborin

    For noon conference today we were lucky to be joined by Dr. Rafael Laniado-Laborin, the head of the Tuberculosis Clinic and Laboratory in Tijuana as well as a Professor in the TJ medical school (Universidad Autónoma de Baja California). He led us though a topic that is highly relevant to our practice – the diagnosis and treatement of multi-drug resistant tuberculosis. He used two cases of real patients from his clinic to highlight alternative regiments available to patients with drug resistant TB strains.

    If you are interested in learning more about this topic and the work Dr. Laniado-Laborin does, check out these lecture recordings from a recent talk he gave to the UCSD ID department. The first lecture focuses on diagnosis and test interpretation, and the second on treatment of MDR-TB.

    MDR-TB Recordings

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    Tuesday Owen Report at Hillcrest

    Today at Owen Report, one of our stellar R2’s, Anna Ter-Zakarian, presented a case of a patient she recently cared for in the ICU. He had advanced HIV with a CD 4 count of 3 (!) and presented with acute shortness of breath, tachypnea and hypoxemia requiring 60 L of 100% oxygen. Chest radiograph revealed diffuse opacifications and blood gas had markedly elevated A-a gradient. A broad infectious work-up was sent and the patient ended up having both Pneumocystis Jiroveci and Cryptococcal pneumonias. 

    Due to the patient’s acute symptoms onset (rather than subacute and gradual as would be expected with these organisms), and recent re-initiation of ART, there was high concern for Immune Reconstitution Inflammatory Syndrome (IRIS). We discussed how IRIS “unmasks” occult and asymptomatic opportunistic infections and why it is important to rule out cryptococcal meningitis. We also discussed that some patients may present with “paradoxical” worsening of inflammatory symptoms even as their OIs are being treated. We also learned that IRIS can unmask undiagnosed autoimmune conditions. Risk factors for IRIS include low CD4 count and high viral loads. The treatment includes steroids as well as ongoing treatment of any underlying OIs and (usually) continuation of ART. 

    Thank you to Dr. Laura Bamford for being our expert discussant and sharing many valuable pearls with our audience!  

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    Owen Report 11/24: Cough and Dyspnea

    This morning we were lucky to be joined by Dr. Darcy Wooten, an amazing HIV Medicine attending and APD of the Infectious Disease Fellowship, to discuss one of her Owen clinic patients.

    The 30-year old man with newly diagnosed HIV presented to our hospital with cough, fevers, chills, night sweats, decreased appetite, and recent weight loss. On admission, the patient had a CD4 count of 102 cell/uL and viral load of 185,000 copies/mL. The CXR revealed a diffuse micronodular/miliary pattern and CT showed upper lobe predominant diffuse ground glass opacities. Initially concerning for TB, the patient’s work-up was significant for elevated serum Coccidiodes IgG antibodies, positive cocci complement fixation with a 1:512 titer, and negative bone scan and spine computerized tomography. The patient was diagnosed with severe pulmonary coccidioidomycosis with presumed dissemination (based on the high titer).

    The patient was treated with amphotericin B for severe cocci and discharged on fluconazole therapy (along with antiretroviral therapy and Bactrim prophylaxis). He could not tolerate the fluconazole and was switched to Posaconazole. The patient subsequently developed severe hypertension refractive to amlodipine, lisinopril, and hydrochlorothiazide. Work up demonstrated low levels of potassium, renin, and aldosterone. The patient was diagnosed with pseudohyperaldosteronism, taken off Posaconazole, and placed on itraconazole and spironolactone, leading to a resolution side effects. The mechanism behind pseudohyperaldosteronism is similar to that of licorice root extract, where steroid synthesis products directly activate mineralocorticoid receptors. Treatment is focused on cessation of Posaconazole and antagonism of the mineralocorticoid receptor with spironolactone.

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    Morning Report 10/13: Inpatient Fever

    This morning one of our stellar resident, Dr. Mandy Mohindra, presented a patient who developed a fever six days into a hospitalization for volume overload. The patient reported a history of worsening chills with rigors, loss of appetite, nausea and vomiting, and fatigue. He had an infiltrated IV with right upper extremity swelling on exam. The patient’s history was significant for liver transplantation three years before (on tacrolimus), diabetes, and severe aortic stenosis. We discussed the decision to start empiric antibiotics, and the workup eventually revealed MRSA bacteremia. The most likely source was the infiltrated peripheral IV.

    We were lucky to have our Infectious Disease expert extraordinaire, Dr. Annie Cowell, to lead us through the management of Staph Aureus bacteremia as we discussed the need to evaluate for potential sites of metastatic MRSA infection.  A wrinkle in our patient’s case was that his blood cultures were persistently positive for MRSA. This prompted a change of antibiotics from vancomycin to ceftaroline and daptomycin and a search for endocarditis. A transthoracic echocardiogram did not reveal valvular vegetations, but a subsequent ECG revealed a new 1st degree heart block. The patient underwent a transesophageal echocardiogram which ultimately demonstrated a paravalvular abscess for which cardiothoracic surgery was consulted. Thank you to all of our resident teams for participating in the discussion. And thank you to Dr. Cowell for adding context to our patient’s clinical course! 

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    Global Health Simulation!

    Mandy Mohindra and Ian Drobish, our inaugural Global Health Pathway residents, participated in an interdepartmental simulation with fellow Emergency, Surgery, and OB/GYN residents. The simulation centered on a patient presenting with profound dehydration from a diarrheal illness. The resident teams had to manage the resuscitation while figuring out the underlying etiology (cholera!) and overcoming a twist – the patient was also pregnant. 

    The teams then participated in a socially distanced debrief and dinner while discussing the realities of providing medical care in under-resourced settings. The session ended with skills stations which taught trainees how to establish intraosseous access (without an EZ-IO device!), calculate fluid drip rates for IV medications, and mix-up homemade oral rehydration solution. Thank you, Ian and Mandy, for representing our program and bringing your A game!