Category Archives: Ask the Expert

Dr. Jade Le talks about West Nile Virus on KERA!

Today on KERA – Dallas affiliate of NPR – Dr. Jade Le from the division of infectious diseases at UT Southwestern talked about West Nile virus and cases already being reported. She provides a quick overview of the infection including individuals who may be at higher risk. Listen to the interview by clicking on the link below!

West Nile Virus Came to Texas Early this Year

Tips for Using Antibiotics Wisely

We will conclude this week with a helpful list of tips from our own ID stewardship experts. Thanks to Dr. Lee, Dr. Cutrell and Dr. Bhavan!

Antibiotics are a precious but finite resource in medicine.  The best way to preserve them for future patients is optimizing antibiotic utilization now.

Ways to use antibiotics wisely include:

  • Avoid antibiotics when not needed
  • Use the narrowest agent possible
  • Ensure the right dose and right route of administration
  • Use the shortest duration of therapy needed
  • Promote antibiotic best practices including an “antibiotic timeout”

Key questions to ask when starting or reassessing antibiotics:

  1. Does my patient really have an infection?
    • Don’t forget to consider non-infectious causes of fever or elevated WBC.
  1. Can I target my therapy for a particular pathogen?
    • Use narrow spectrum agents to target positive culture results.
    • If no culture data available, the lack of patient risk factors for drug-resistant pathogens (like MRSA or Pseudomonas) may allow safe de-escalation to narrower agents.
  1. Are there patient factors that impact antibiotic dosing?
    • Changes in renal or hepatic function
    • Drug-drug interactions, esp. with oral abx that may impair absorption
    • Don’t hesitate to contact your pharmacist or stewardship team for help!
  1. How long do I need to treat this infection?

As always, the Antimicrobial Stewardship Programs at each hospital are available to help with these questions, so please contact us at any time.

Kavita Bhavan- Parkland

Brad Cutrell- VA

Francesca Lee- UTSW

Fever of Unknown Origin

“The mark of a good ID clinician is not how many antibiotics he or she starts but how many he or she stops.” — Brad Cutrell

Definitions

  • “Classic” definition of FUO
    • Fever > 38.3 C
    • Duration > 3 weeks
    • Unknown etiology after > 1 week hospital evaluation
  • Revised Classification: proposed revisions decreased duration and removed inpt evaluation criteria
    • šClassic Definition: temperature higher than 38.0 °C (100.4 °F) for more than 3 weeks and either more than 3 days of hospital investigation or more than two outpatient visits without determination of the cause.š
    • Health care–associated FUO: temperature higher than 38.0 °C (100.4 °F) for more than 3 days in a hospitalized patient receiving acute care with infection not present or incubating on admission.
    • šImmune-deficient (neutropenic) FUO: štemperature higher than 38.0 °C (100.4 °F) in a patient in with ANC < 500 in whom the diagnosis remains uncertain after more than 3 days despite appropriate investigation, including at least 48 hours’ incubation of microbiologic cultures.
    • šHIV-related FUO: temperature higher than 38.0 °C (100.4 °F) in a patient with confirmed HIV infection for more than 3 weeks in outpatients or more than 3 days in inpatients.

Epidemiology

  • Classic FUO etiologies fall into 5 major categories: Infection, Malignancy, Inflammatory, Miscellaneous, Unknown
  • Distribution depends on decade, patient age, geography, and type of practice
  • Classic FUO Epid
  • Classic FUO Epi Trends

Etiology

  • Infections
    • Tuberculosis (extrapulmonary, miliary, IC hosts)
    • Occult abscess (abd/pelvic)
    • Complicated UTI
    • Osteomyelitis
    • Culture-negative endocarditis
    • Malaria
    • Typhoid fever
    • Visceral Leishmaniasis
  • Malignancies
    • Lymphoma (esp. NHL)
    • Leukemia
    • Renal Cell carcinoma
    • Hepatocellular carcinoma or liver metastases
  • Inflammatory Disorders
    • Adult-onset Still’s Disease
    • RA
    • SLE
    • Temporal arteritis (Giant Cell arteritis)
    • Polymyalgia rheumatica
  • Miscellaneous
    • Drug Fever (abx, anti-seizure meds, NSAIDs, anti-arrhythmics)
    • Alcoholic hepatitis
    • Venous thromboembolic disease
    • Endocrine disease (hyperT, adrenal insufficiency, pheo)
    • Disordered heat homeostasis (“central fever”)
    • Factitious Fever (Munchausen)
  • Special Populations
    •  Pediatrics
      • Infectious most often, particularly viral and respiratory
      • CTD: Kawasaki in younger, AOSD in older children
    •  Geriatrics
      • CTD (GCA and PMR) and malignancy more common than in < 65 age group
    • Returning Traveler
      • Malaria, typhoid fever, amebic liver abscess, acute HIV

Diagnostic Evaluation

  • History and Physical!
    • Recent prospective Dutch series found average of 10.5 potential diagnostic clues per pt from history/exam and only 3 per pt from lab testing (81% misleading)
    • Dx
  • Laboratory Testing
    • Best guided by history/exam clues, not “shotgun” approach
    • Laboratory testing yields diagnosis in 25% of cases
    • Labs
  •  Imaging
    • CXR and CT abdomen/pelvis part of initial tests
    • MRI/MRA good for CNS, spine, and vasculitis evaluation
    • Older nuclear tagged scans and Gallium scans have been largely replaced by FDG-PET scans
    • Recent meta-analysis showed pooled sens. 98% and spec. 86% for FDG-PET, arguing for role if initial w/u negative
  • Invasive Testing
    • BM evaluation useful, especially if abnormal CBC or immunocompromised host
    • Biopsy of sites with suspected involvement in select cases

Management and Prognosis

  • Management
    • Therapeutic trials of abx generally not recommended
    • “Non-specific Rx rarely cures FUO but may delay Dx.”
    • Exceptions: empiric steroids for suspected GCA or empiric abx in neutropenic patients
  • Prognosis
    • Depends on age and etiology of FUO (worse with elderly and malignancy as etiology)
    • Most without Dx after extensive evaluation have good prognosis with low mortality and fever resolution
  • Remember: The cause is more likely a common diagnosis presenting in an atypical fashion than a rare disease presenting in a typical fashion.
  • FTMO

#clinicalpearls Cardiology

EDITED (thank you to Dr. Khera!):

Indications for operative repair of aortic regurgitation:

  1.  CHF symptoms (OR evidence that the ventricle is decompensating)
  2. Asymptomatic, but EF 50mm (Class IIa, probably should)
  3. Asymptomatic, LV end systolic diameter > 50mm (Class IIa, probably should) – (#2 and #3 make the “rule of 50’s”)

Ask the Expert: Dr. Bedimo on HCAP

You are on call and get a call from the ER for possible pneumonia in a patient that resides in a nursing home. How do you approach the choice of antibiotic therapy? Should this be treated as community-acquired pneumonia, or health-care associated pneumonia?

Dr. Bedimo, Chief of the Infectious Disease Division at the North Texas VA Medical Center, notes the following: “The ATS/IDSA guidelines indeed include nursing homes in the definition of Health Care Associated Pneumonia (Am J Respir Crit Care Med. 2005;171(4):388).

Healthcare-associated pneumonia (HCAP) is defined as pneumonia that occurs in a non-hospitalized patient with extensive healthcare contact, as defined by one or more of the following:

  • Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days
  • Residence in a nursing home or other long-term care facility
  • Hospitalization in an acute care hospital for two or more days within the prior 90 days
  • Attendance at a hospital or hemodialysis clinic within the prior 30 days

However, the issue is whether these settings indeed increase the likelihood of multi-drug resistant pathogens such as MRSA and MDR Pseudomonas.  The above guidelines are dated, and there’s recent controversy over the topic.  So, newer guidelines (due anytime now) might change to likely exclude nursing home residents without recent hospital contact…”

 

 

Sepsis: More Complicated Than We Think

Yesterday at noon conference, Dr. Cutrell (Infectious Disease Division), referred to several articles that have reexamined sepsis including its mechanisms and management. Check out the articles below that Dr. Cutrell referred to:

Article written by Dr. Suffredini and Dr. Munford (former UTSW resident and faculty) in JAMA from 2011 reviewing past therapies for sepsis and potential future projects:

http://www.ncbi.nlm.nih.gov/pubmed/21750297

Article written in Proceedings of the National Academy of Sciences in the United States of America in 2013 that reevaluates the utility of murine models in understanding human diseases. Followed by a link from The New York Times that addresses this same topic:

http://www.ncbi.nlm.nih.gov/pubmed/23401516

http://www.nytimes.com/2013/02/12/science/testing-of-some-deadly-diseases-on-mice-mislead-report-says.html?pagewanted=all

Big thanks to Dr. Cutrell for the links!

Q&A with Dr. Mansi

Dr. Ishak Mansi is professor in the department of medicine and clinical sciences and in the division of outcomes and health services research at UT Southwestern. He recently gave Grand Rounds and talked about studies looking at adverse events related to statins. Below is a short Q&A with Dr. Mansi as he talks about why he became interested in outcomes research and what constitutes a good study.

Q: What made you get interested in outcomes research?

I am a clinician, who practiced medicine since my graduation 33 years ago; therefore, as I interact with my patients, listen, and note their perspectives and concerns, I wonder about many of our practices and their actual impact on meaningful patients’ clinical outcomes.

We have to admit that we do “weird stuff” in the site of lay people: think about giving patients a strange looking pill that may cause symptoms and costs money, while they have no specific complaint (e.g. statins in primary prevention).


Q: Why are you interested in statin therapies and their outcomes?

I was exposed in my career to two extremes of statins utilization. The first was in Louisiana State University Health Science Center in Shreveport (LSUHSC), where patients rarely filled statin prescriptions. In LSUHSC, the institute did not have an outpatient pharmacy and our patients were too poor to afford paying for statins.

The second was in the Brooke Army Medical Center, where statins were available for free for all their population. Frequently, patients LDL-cholesterol levels were collected through electronic medical records, and were considered as quality of care measures for primary care providers. Therefore, physicians liberally prescribed statins to avoid being penalized as “poor-performers”. Living these two extremes challenged my thoughts and elicited my interest about the actual benefit/harms from these medications.  


Q: What are the characteristics/features of a well designed study that looks at outcomes? (Ex. Large cohort, prospective versus retrospective)

Clinical trials are the gold standard in establishing medication efficacy (does this drug work?); but it should be followed by other studies that establish medication effectiveness (how well this medication actually works in clinical practice for a target population). Additionally, observational studies should guide the design of future clinical trials to ensure appropriate design. In general, prospective cohort studies are better than retrospective studies, but they are also much more expensive, time consuming, and require many years before obtaining results.

A well-designed study is the one that considers all known information about a problem and sincerely attempt to answer the question at-hand, rather than attempting to prove a “premeditated outcome”  that serves a private interest.

AS? What about TAVR!

Gualano

A constant topic of discussion in Cardiology, transcatheter aortic valve replacement (TAVR) is minimally invasive surgical procedure repairs the valve without removing the old, damaged valve. The UT Southwestern TAVR team is a multidisciplinary group composed of interventional cardiologists, imaging specialists, cardiothoracic surgeons, echocardiography technicians, and many other members. Dr. Sarah Gualano, interventional cardiologist at the UT Southwestern University Hospital, was featured on NPR’s Vital Signs on November 3rd; hit the link below to hear about the TAVR program here at UTSW.

KERA Listen

Ask the Expert – Nausea/Vomiting

Dr. Elizabeth Paulk:

Nausea is a prevalent symptom, especially in patients at the end of life. Up to 68% of cancer patients experience nausea during the course of disease, and 13-17% suffer from it in the last weeks of life. Around 45% of AIDS patients, 17-48% of heart disease patients, and 30-43% of end-stage renal disease patients are nauseated. There are no formal, evidence-based guidelines available for nausea management, put the key principles are:

1. Treat the nausea based on the underlying etiology

2. Remember that there are many neurotransmitters involved, so use “dirty” drugs that affect many different ones. Promethazine, for example, is anticholinergic, antihistaminic, and mildly anti-dopaminergic.

3. Your strategy should be similar to the management of hypertension – stack the drugs up. Once the nausea is controlled, you can start eliminating agents. Often patients will require two or more agents for control.

The way to remember how to treat nausea is the acronym, VOMITS

  • Vestibular Causes (acetylcholine and histamine) –> scopolamine patch or promethazine
  • Obstruction of Bowel by Constipation (this does not apply to complete bowel obstruction – see below) (acetylcholine, histamine, and likely serotonin 3) –> start with a drug that stimulates the myenteric plexus, like senna, and escalate as needed.
  • dysMotility of upper gut (cholinergic, histaminic, 5HT3, 5HT4) –> Use prokinetics which stimulate 5HT4 receptors, like metoclopramide
  • Infection, Inflammation (Cholinergic, Histaminic, 5HT3, Neurokinin 1) –> Promethazine (e.g. for labyrinthitis), prochlorperazine, aprepitant
  • Toxins stimulating the chemoreceptor trigger-zone in the brain such as opioids (Dopamine 2, 5HT3) –> Prochlorperazine, Haloperidol, Ondansetron
  • Scared (for those with severe anxiety or anticipatory nausea) –> benzodiazepines like valium can be very helpful, but should not be used as monotherapy.

Tips:

  • Remember that dexamethasone is also a powerful anti-emetic, and if you are not having success with the strategies above, consider it as an additional agent.
  • Promethazine and prochlorperazine are very different drugs. Promethazine is most useful for vertigo and gastroenteritis due to infections and inflammation. Prochlorperazine is preferred for opioid related nausea.
  • For complete bowel obstruction, the primary management strategy is bowel rest. Octreotide is very helpful in this context.

Ask the Expert: HIV Treatment and Pregnancy

Continuing the series of “Ask the Expert”, Dr. James Cutrell, Assistant Professor in the Department of Medicine Infectious Disease Division, comments on treatment of HIV patients who are pregnant. A topic that is definitely high-yield in preparation for internal medicine boards. Below are Dr. Cutrell’s comments:

“Here is a link to the most recent guidelines on HIV and pregnancy published in March of this year.  This is the summary of the major changes with links to the full guidelines and different sections.

http://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0/

The following are the key take home points for the residents:

  • All HIV-infected women should be virally suppressed on ART if contemplating pregnancy.
  • All HIV-infected women, either known or newly diagnosed, should be started on ART regardless of CD4 count to achieve maximal viral suppression prior to delivery and to reduce perinatal transmission of HIV.
  • IV zidovudine (AZT) is only administered intrapartum to mothers with a detectable VL > 1,000 copies/mL at time of delivery or if rapid HIV Ab screen is positive and confirmatory testing is pending.
  • Due to increased experience and longitudinal safety data, several additional ART drugs have been added to the preferred regimens in pregnancy in addition to the traditional combination of zidovudine-lamivudine and lopinavir-ritonavir.
    • NRTI: Tenofovir plus emtricitabine or Abacavir plus lamivudine
    • PI: Ritonavir-boosted atazanavir
    • NNRTI: Efavirenz only after first 8 weeks of pregnancy
  • Historically, efavirenz use has been discouraged in women of child-bearing age due to potential teratogenicity.  Although current data does not suggest a significant increase in birth defects, an increase in neural tube defects from 1st trimester exposure could not be completely excluded due to small numbers.   The US Guidelines state that women of childbearing age should have a pregnancy test and be counseled to use contraception and avoid pregnancy prior to starting efavirenz based regimens.  Women who are pursuing pregnancy should be treated with alternative regimens if possible.  However, the period of risk for the fetus is only in the first 6-8 weeks (1st trimester) which usually has past before a pregnancy is recognized; therefore, a woman who is beyond the 8 week period can be started on an efavirenz-based regimen if ART-naïve or can continue it if she is already on efavirenz and virologically suppressed and has become pregnant.
  • The UK and WHO guidelines do not recommend restrictions on the use of efavirenz in pregnancy or women desiring to have children.