Between the ongoing COVID-19 pandemic, a new baby, a move and starting two new jobs, I haven’t had the time to keep this website going (as I am sure many have noted). The COVID-19 page has not been updated but at this time, there are plenty of other resources available that summarize the relevant and updated literature.
As of now, I am not sure when I will have the time to dedicate to this site. However, I do plan to get back to it one of these days. In the meantime, its my 2022 New Years resolution to remain more active on Twitter (@foamid) and continue to bring small clinical ID pearls. See you there!
There’s so much information about the novel coronavirus COVID-19 on the internet that it is hard to keep up with the onslaught of information. We wanted to compile the ultimate list of reputable resources for clinical providers to access when they need to, at a moment’s time.
Since information on COVID-19 is rapidly changing, these resources are not specific papers or blog posts, but rather websites that are maintaining up to date information on epidemiology, pathophysiology, and management. Resources span all types, including website behemoths like the WHO and CDC, as well as twitter accounts for people who get their news from social media.
Since this is an ultimate list but we don’t pretend to have ultimate knowledge of all resources, please send us resources that we may have missed and we will add them on here! We also acknowledge that this list is U.S. centric because we are from the States, but we would love input on resources for other countries so we can make this a more international list.
Sanford Guide – quick but detailed practical clinical overview of everything you need to know about COVID-19 when you’re taking care of patients with COVID-19
Infectious Diseases Society of America – resource center includes clinical guidelines, recommendations, and up to date payment coverage (!) for COVID-19 treatment
University of Washington – the holy grail of practical documents developed by people who are currently battling a COVID-19 outbreak. All documents can be utilized by others and adapted for their own institutional protocols.
IDStewardship – a very thorough, but easily read overview of potential treatment options for COVID-19 and how/when to use them
University of Liverpool – charts on drug drug interactions with experimental therapies for COVID-19
CIDRAP – focuses on the health policy aspect of COVID-19 news
Society of Critical Care Medicine – online training modules for disaster medicine, resource availability in U.S., and other fantastic resources for front-line clinical providers
ClinicalTrials.gov – a currently-recruiting randomized controlled trial of remdesivir for COVID-19 treatment
CURE ID – an FDA and NIH supported website where you can report and see new uses of existing drugs for difficult-to-treat infectious diseases. Download their mobile app too!
Blogs:
Virology Blog– blog run by virologists with recent discussions on COVID-19
ScienceSpeaks– global ID news blog written by physicians
ChasingMicrobes.com – a weekly update on COVID-19 literature compiled by the Boston Children’s Hospital pediatric Infectious Diseases fellows
This Podcast Will Kill You – Two epidemiologists (both named Erin) provide you with an entertaining summary of new COVID-19 knowledge, alongside a recipe for a Quarantini and a Placeborita.
Learning about fungi is hard enough even for infectious disease fellows (Narrator: especially for infectious disease fellows). By the time you learn how to differentiate the yeasts from the molds, the fungi kingdom decides to throw you a curve ball: Enter the shape shifters into the game of fungi learning – the dimorphic fungi.
The Dimorphic fungi shape shift depending on the weather (literally). They exist as molds in the great outdoors (environmental temperatures) and yeasts in the great indoors (inside our bodies at body temperatures). Clinically, this also means you will see the yeast forms in a histopathology review of a tissue sample, and our friends in the microbiology lab can re-create the environmental factors to grow them out as mold forms in culture. So essentially, they also shape shift between the microbiology lab and the pathology department. (They are sneaky Fung(uy)i…).
This shape shifter differs from others in that it does not shape shift by temperature but resembles other shape shifters in that it exists as a mold in the environment and a spherule (Image) inside the body.
Spherules are round, and contain endospores which are uninucleate and have walls and cytoplasmic inclusions
Can be mistaken for yeast if only endospores are seen (but endospores don’t bud like yeasts!)
Geography, Reservoir and Mode of Transmission
Endemic in southwest of the US and certain arid regions in South America
In the US, highest incidence in Arizona and California
Reservoir includes: soil (increased during dry periods after rain/storms/earthquakes or excavation work)
Mode of transmission: aerogenic
Race predilection: Filipino and African Americans at higher risk for disseminated disease (Board favorite!)
Clinical presentation
Two-thirds of individuals remain asymptomatic or develop self-limiting respiratory symptoms. When symptomatic → pulmonary involvement in >95% of cases(2)
The disease can spread hematogenously to the following extrapulmonary sites: skin, soft tissue, skeleton, CNS (both meninges and spinal cord), eyes, heart, liver, kidneys, and prostate(1)
Primary presentation often associated with skin findings (erythema nodosum, erythema multiforme) and rheumatological findings (myalgia, arthralgia)(2)
Eosinophilia is often present!
Unlike pulmonary nodules in histoplasmosis that often calcify, nodules in coccidiomycosis become small ‘grapeskin’ cavities, and cavities are often thin walled and can be associated with pleural effusions(3)
Diagnosis
Your friendly Infectious disease doctors will always ask for tissue, and if classic spherules are seen in histopathology or culture confirms growth, that’s a slam dunk diagnosis! But we understand that is not always feasible, so in addition to clinical history + presentation, in order of importance:
Tissue/culture
Serology (keeping in mind that it can be false negative very early on in the disease)
Culture:
*Please alert the microbiology lab if you suspect coccidiomycosis and are sending them cultures! (culture needs to be specially handled in the lab due to the risk occupational transmission/infection — just like all dimorphic fungi covered in this review series).
Confirms diagnosis, growth usually detected 4-5 days (4)
Histopathology:
Presence of endospore-containing spherules is diagnostic (see Image, Morphology)
Tissue eosinophilia may be present, and as endospores mature into spherules,
Granulomatous reaction predominates
Antigen detection:
Urinary antigen not widely used, however urinary histoplasma antigen test could be positive in 50% of cases(4)
Serology:
IgM usually becomes detectable within 1-3 weeks therefore negative serology early in the disease doesn’t rule out the disease
IgG becomes detectable anywhere between 3rd/4th week to several months after becoming infected. This usually reflects degree of infection and can be used to monitor the disease(4)
Increasing titers (or titers >1:32) may suggest dissemination(4)
Molecular methods:
No commercially available tests
Management(5)
Pulmonary disease:
Mild pulmonary disease: no treatment
Asymptomatic nodule/cavity: no treatment
Symptomatic chronic cavity: fluconazole/itraconazole (at least) for 12 months
Extra-pulmonary disease:
Soft tissue/bone: fluconazole/itraconazole (at least) for 12 months (*except for severe disease → Lipid Amphotericin B as an initial therapy for about 3 months)
References:
Walsh TJ, Hayden RT, and Larone DH. Larone’s medically important fungi, 6th edition. ASM Press, 2018.
Salzer HJF, Burchard G, Cornely OA, et al. Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease. Respiration. 2018; 96(3):283-301.
Knox KS. Letter to the Editor: Perspective on Coccidioidomycosis and Histoplasmosis. Am J Resp Crit Care Medicine. 2014; 189(6):752-753.
Saubolle MA, McKellar PP, and Sussland D. Epidemiologic, clinical, and diagnostic aspects of coccidiomycosis. J Clin Microbiol. 2007; 45(1):26-30.
Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016; 63(6):e112–e146
Learning about fungi is hard enough even for infectious disease fellows (Narrator: especially for infectious disease fellows). By the time you learn how to differentiate the yeasts from the molds, the fungi kingdom decides to throw you a curve ball: Enter the shape shifters into the game of fungi learning – the dimorphic fungi.
The Dimorphic fungi shape shift depending on the weather (literally). They exist as molds in the great outdoors (environmental temperatures) and yeasts in the great indoors (inside our bodies at body temperatures). Clinically, this also means you will see the yeast forms in a histopathology review of a tissue sample, and our friends in the microbiology lab can re-create the environmental factors to grow them out as mold forms in culture. So essentially, they also shape shift between the microbiology lab and the pathology department. (They are sneaky Fung(uy)i…).
At 25°C-30°C (mold form): septate hyphae with short or long conidiophores where a pear-shaped conidia form at the apex of the conidiophore (has a lollipop-like appearance). (Image A)
At 37°C (yeast form): appear as yeast-like cells, thick walled and budding with a broad base (Image B)
Geography, Reservoir and Mode of Transmission:
Endemic in North America (Ohio & Mississippi river valleys and the Great Lakes region)
Sporadic cases in Africa and India(2)
Reservoir includes: moist soil with decaying vegetative matter, decomposed wood
Mode of transmission: aerogenic, skin inoculation
Clinical presentation:
Incubation period: 30-45 days (3)
Spectrum of clinical disease:
Asymptomatic disease – occurs in ~50% of individuals
Acute pulmonary blastomycosis – resembles community-acquired pneumonia with variable presentation (infiltrates, consolidation +/- cavitation, reticulonodular patterns, small pleural effusions)(4)
Chronic pulmonary blastomycosis – can mimic presentation of TB, lung cancer, and histoplasmosis. Radiographic pattern often is described as alveolar or fibronodular infiltrations, mainly with an upper lobe distribution. Absence of mediastinal lymph node involvement in blastomycosis can distinguish it from Histoplasmosis.(4)
Extrapulmonary disease have been described in two-thirds of patients with chronic blastomycosis(3). Most frequent sites: skin, bones and genitourinary system.
Patients frequently present with cutaneous lesions without clinically active pulmonary disease.
CNS involvement is rare, except in immunocompromised hosts. As many as 40% of AIDs patients who have blastomycosis have CNS disease (mass lesions or meningitis)(5).
Diagnosis:
Your friendly Infectious disease doctors will alwaysask for tissue, and if classic broad-based budding yeast are appreciated in histopathology, that’s a slam dunk diagnosis! But we understand that is not always feasible, so in addition to clinical history + presentation, in order of importance:
Tissue (histopathology, faster visualization, culture will have a long incubation time)
Urine Antigen detection (keeping in mind issues with cross-reactivity as outlined below)
Culture:
*Please alert the microbiology lab if you suspect Blastomycosis and are sending them cultures! (culture needs to be specially handled in the lab due to risk occupational transmission/infection (just like all dimorphic fungi covered in this review series).
Most sensitive method, however long incubation time
For cutaneous lesions, important to obtain specimen from active leading edge
High sensitivity for urine detection (93%) in largest published evaluation(2) but low specificity (79%) due to cross reactivity with Histoplasmosis, Paracoccidioidomycosis and Talaromycosis (previously known as penicilliosis)
Serology:
No role in diagnosis because of poor sensitivity and high cross-reactivity(4)
Molecular methods:
No commercially available tests
Management(3):
Pulmonary disease
Mild to moderate: Itraconazole 6-12 months
Moderate to severe: Lipid Amphotericin B for 1-2 weeks followed by → Itraconazole for 6-12 months
Disseminated disease
Mild to moderate: Itraconazole for 6-12 months
Moderate to severe: Lipid Amphotericin B for 1-2 weeks followed by → Itraconazole for 12 months
References: 1. Walsh TJ, Hayden RT, Larone DH. Larone’s medically important fungi, 6th edition, ASM press, 2018. 2. Saccente M and Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23:367–381. 3. Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Jun 15;46(12):1801-12 4. Salzer HJF, Burchard G, Cornely OA, et al. Diagnosis and management of systemic endemic mycoses causing pulmonary disease. Respiration; 2018;96:283–301. 5. Pappas PG, Pottage JC, Powderly WG, et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Ann Intern Med;1992:116
Learning about fungi is hard enough even for infectious disease fellows (Narrator: especially for infectious disease fellows). By the time you learn how to differentiate the yeasts from the molds, the fungi kingdom decides to throw you a curve ball: Enter the shape shifters into the game of fungi learning – the dimorphic fungi.
The Dimorphic fungi shape shift depending on the weather (literally). They exist as molds in the great outdoors (environmental temperatures) and yeasts in the great indoors (inside our bodies at body temperatures). Clinically, this also means you will see the yeast forms in a histopathology review of a tissue sample, and our friends in the microbiology lab can re-create the environmental factors to grow them out as mold forms in culture. So essentially, they also shape shift between the microbiology lab and the pathology department. (They are sneaky Fung(uy)i…)
This is the first post out of 6 and will focus on our first shapeshifter, Histoplasma capsulatum.
*Please alert the microbiology lab if you suspect histoplasmosis and are sending them cultures! (culture needs to be specially handled in the lab due to risk occupational transmission/infection (just like all dimorphic fungi covered in this review).
Sensitivity of both tissue and blood cultures depend on the presentation (pulmonary vs. disseminated), immune status and burden of disease(5)
Disseminated disease → ~74% will have positive cultures(6)
Pulmonary disease → ~42% will have positive cultures(6)
HIV/AIDS patients: → ~ 90% of respiratory cultures will be positive(7) →~50% of blood cultures will be positive(7)
2. Histopathology:
Appear as yeast form, predominantly phagocytosed within macrophages and histiocytes
Presence in tissue supports diagnosis, although does not necessarily indicate active infection (could be detected in non-active granulomas for years)
Characteristic pathology feature is the presence of granulomas (caseating or non-caseating)(6)
In HIV/AIDS patients with disseminated disease, Histoplasma antigen can be detected in 95% of cases
Mediastinal involvement in histoplasmosis (mediastinal granuloma, mediastinitis) doesn’t usually result in positive antigen testing
Histoplasma antigen can cross react with all the dimorphic fungi covered in this review series (less commonly for coccidioides spp.)
4. Serology:
Antibodies take 4-8 weeks to become detectable therefore not useful for acute diagnosis but can be helpful for subacute and chronic forms of the disease
Titers usually decrease with disease resolution, but slowly so titers cannot be used to monitor for treatment response
Immunocompromised patients, particularly those with humoral defects, might not mount an antibody response so serology testing isn’t as useful.
5. Molecular methods:
No currently FDA approved molecular assay for H. capsulatum for clinical use.
PCR assays available in reference labs but are not yet standardized
Management(12):
Clinical presentation
Mild/Moderate
Moderate/Severe
Chronic
Pulmonary
<4weeks: none >4weeks: itraconazole for 6-12 months
Lipid amphotericin B for 1-2 weeks followed by itraconazole for 12 weeks
Itraconazole for 12 months
Disseminated
Itraconazole for 12 months
Lipid amphotericin B for 1-2 weeks followed by itraconazole for 12 months
N/A
References: 1. Climate change: the role of the infectious disease community. Lancet Infect Dis. 2017; 17:1219. 2. Greer A, Ng V, and Fisman D. Climate change and infectious diseases in North America: the road ahead. CMAJ. 2008; 178:715–722. 3. Walsh, TJ, Hayden, RT, and Larone, DH. Larone’s medically important fungi, 6th edition, ASM press, 2018. 4. Queiroz-Telles F, Fahal AH, Falci DR, et al. Neglected endemic mycoses. Lancet Infect Dis. 2017;17:e367–e377. 5. Azar MM and Hage CA. Laboratory Diagnostics for Histoplasmosis. J Clin Microbiol. 2017; 55:1612–1620. 6. Hage CA, Azar MM, Bahr N, Loyd J, and Wheat LJ. Histoplasmosis: up-to-date evidence-based approach to diagnosis and management. Semin Respir Crit Care Med. 2015; 36:729–745. 7. Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007;20:115–132. 8. Hage CA, Ribes JA, Wengenack NL, et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis. 2011;53:448–454. 9. Wheat LJ and Kauffman CA. Histoplasmosis. Infect Dis Clin North Am. 2003;17:1–19. 10. Swartzentruber S, Rhodes L, Kurkjian K, et al. Diagnosis of acute pulmonary histoplasmosis by antigen detection. Clin Infect Dis. 2009; 49:1878–1882. 11. Saccente M and Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23:367–381. 12. Wheat LJ, Freifeld AG, Kleiman MB, et al; Infectious Diseases Society of America. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807–825.
Learning about fungi is hard enough even for infectious disease fellows (Narrator: especially for infectious disease fellows). By the time you learn how to differentiate the yeasts from the molds, the fungi kingdom decides to throw you a curve ball: Enter the shape shifters into the game of fungi learning – the dimorphic fungi.
The Dimorphic fungi shape shift depending on the weather (literally). They exist as molds in the great outdoors (environmental temperatures) and yeasts in the great indoors (inside our bodies at body temperatures). Clinically, this also means you will see the yeast forms in a histopathology review of a tissue sample, and our friends in the microbiology lab can re-create the environmental factors to grow them out as mold forms in culture. So essentially, they also shape shift between the microbiology lab and the pathology department. (They are sneaky Fung(uy)i…)
Some of the clinically relevant dimorphic fungi have a predilection for geographical location (endemic mycoses), and therefore are very popular in board exams to the dismay (or joy, after this review series?) of medical trainees.
#ClimateChangeIsReal isn’t just pertinent in the political arena, but also for these endemic fungi. The grave consequences of climate change might change and expand the geographical distribution(1,2) of these fungi and therefore result in more catch-up learning on our end. This is almost akin to learning the constant re-classification and re-naming of the fungi kingdom (thanks, no thanks taxonomists…)
In this review series, I will go over the endemic fungi in a ‘high yield’ approach that will hopefully be pertinent for both shelf exams/boards and clinical practice.
I’ve also purposefully made it a two-pager/per fungi review (or 1 pager if you print it double-sided, #SaveTheTrees). We will be providing PDF links with every Fungi review. This will be an easy reference for a pocketbook, handouts to print to teach your medical students or if you want to flex your knowledge of endemic fungi during rounds (All win-win-win situations!)
The profile of each shape shifter will be released every Friday in the spirit of #FungalFriday. The dimorphic fungi that will be covered during the #ShapeShifterSeries include:
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Talaromycosis
Paracoccidiomycosis
Sporotrichosis
Our First Shape shifter in the series to be released this coming #FungalFriday will be Histoplasmosis, aka the Ohio valley disease/Cave disease. What does Ohio or caves for the matter have to do with this Fungus? Find out more this coming Friday!
Fatima Al Dhaheri, MBBS The Fung(uy)i squad
References: 1. The Lancet Infectious Diseases. Climate change: the role of the infectious disease community. Lancet Infect Dis. 2017;17:1219. 2. Greer A, Ng V, Fisman D. Climate change and infectious diseases in North America: the road ahead. CMAJ. 2008;178:715–722.
[This post was written by Ahmed Abdul Azim, a senior infectious disease fellow at Beth Israel Deaconess Medical Center]
During the fall and winter season, you are likely to see a few cases of viral meningitis. Even though viral encephalitis is less common, it is important to try to differentiate these clinical entities as a clinician, since they carry different prognoses. (The bulk of this review is adapted from Mandell, Douglas and Bennett’s principles and practice of infectious diseases)1
Cerebral spinal fluid analysis
Before we go any further, let’s briefly review cerebral spinal fluid findings on lumbar puncture for different syndromes:
WBC(cells/mm3)
Primary cells
Glucose(mg/dL)
Protein(mg/dL)
Viral
50-1000
Lymphocytic
>45
<200
Bacterial
1000-5000
Neutrophilic
<40
100-500
Mycobacterial
50-500
Lymphocytic
<45
50-300
Cryptococcal/fungal
20-500
Lymphocytic
<40
>45
Important points to consider: · Bacterial meningitis: 10% of cases have a lymphocyte predominant CSF cell analysis · WNV encephalitis: over a 1/3 of patients with WNV encephalitis had neutrophil predominant CSF pleocytosis · Enteroviruses: CSF analysis done early in illness course may yield neutrophil predominant pleocytosis in 2/3 of cases – generally will convert to lymphocytic predominant if repeated in 12-24 hours.
Take home point: always interpret CSF within the clinical context in front of you!
CSF to serum glucose ratio of < 0.4 is suggestive of bacterial meningitis
Traumatic LP may cause elevated CSF protein: for every 1000 RBC/mm3, subtract 1 mg/dL protein
Traumatic LP may cause elevated CSF WBC: for every 500-1000 RBC/mm3, subtract 1 WBC/mm3
RBC Adjustment for WBC in CSF = Actual WBC in CSF – (WBC in blood x RBC in CSF/RBC in blood)
Viral meningitis versus encephalitis
Both syndromes often present with a triad of2: (1) FEVER (2) HEADACHE and (3) ALTERED MENTAL STATUS However, the trick is to explore the history and signs further. Epidemiological clues include:
travel history
prevalence of disease in the local area
occupational exposure
animal and insect exposure
immunization history
underlying immune status
Patients with viral encephalitis: tend to have diffuse cerebral cortex involvement with abnormal cerebral function – Symptoms: altered mental status, motor/sensory deficits, altered behavior and/or personality changes, speech and/or movement disorders
Patients with viral meningitis: DO NOT have diffuse cerebral cortex involvement → cerebral function IS INTACT – Symptoms: headache, lethargy, neck stiffness/pain
Patients with meningoencephalitis: tend to have a combination of meningitis and encephalitis symptoms
Regardless, if a patient has symptoms and/or signs of meningitis or encephalitis, a lumbar puncture can be helpful.
Viral Meningitis – Common Pathogens
Overall, most cases of aspectic meningitis syndromes are caused by viruses
1. Enteroviruses (e.g. Coxsackie, echovirus, other non-polio enteroviruses) – by far the most common cause of viral meningitis/aseptic meningitis3
Summer/fall seasons (less commonly in the winter)
Clinical manifestations:
abrupt onset fever
headache
vomiting/diarrhea
photophobia
malaise
+/- meningismus
Think of enterovirus viral meningitis in patients when rash and/or diarrhea is present
CSF analysis done early in illness course may yield neutrophil predominant pleocytosis in 2/3 of cases – generally will convert to lymphocytic predominant if repeated in 12-24 hours4.
Take home point: always interpret CSF within the clinical context in front of you!
2. Herpes virus simplex viral meningitis – usually caused by HSV-2 >> HSV-18
Only accounts for 0.5-3% of viral meningitis/aseptic meningitis cases9
Typically mild symptoms
80% with HSV-2 genital lesions/ulcers up to 1 week prior to presenting with viral meningitis
Patients with a clinical picture consistent with aseptic meningitis and have HSV isolated in CSF will end up having HSV-2 in 95% of cases. This is a self-limited illness3
3. West Nile Virus – more likely to cause an encephalitis syndrome. Yet, may present with aseptic meningitis or asymmetrical flaccid paralysis10
Viral Encephalitis – Common Pathogens
A cause is identified in approximately 36-63% of cases10,11
Causes of encephalitis (Most common to least common in US study of patients that met criteria for encephalitis)12:
Viruses (70%)
Enteroviruses: 25%
HSV-1: 24%
Varicella zoster virus (VZV): 14%
West Nile virus (WNV): 11%
EBV: 10%
Others: 16%
Bacteria (20%)
*In a study of HIV uninfected patients, viruses caused up to 38% of cases, followed by bacterial pathogens at 33%, Lyme disease at 7%, and fungi at 7%. Syphilis was identified as the culprit in 5% of cases, and mycobacterial infections at 5%, while prion disease was responsible for 3% of cases of encephalitis11
1. HSV encephalitis: most common cause of encephalitis in the US (1/250,000 population annually). HSV-1 accounts for greater than 90% of HSV encephalitis in adults13. Fewer than 6% of CSF PCR cases had a “normal” neurological exam14.
> 96% have CSF pleocytosis14,15,16
Protein is elevated; glucose is normal 95% of the time14,15,16
MRI > CT, revealing changes of temporal lobes in ~89% of cases confirmed by CSF PCR15
CSF PCR is highly sensitive and specific, with an excellent positive and negative predictive value17
If HSV encephalitis is suspected and PCR is negative, repeat HSV PCR testing in 3-5 days
HSV PCR remains positive up to 7 days in 98% of cases after onset of symptoms
Treatment: IV acyclovir is the treatment of choice; call your nearest ID colleague for help
Mortality in acyclovir-treated patients stratified by age group18:
11% in < 2 year olds
22% in 22-59 year olds
62% in > 60 year olds (initial level of consciousness strongly predicted mortality16)
2. West Nile Virus encephalitis: transmitted via a mosquito (vector) bite, currently the most common cause of epidemic viral encephalitis nationally19
Most are asymptomatic (80%); macular rash in up to 50% of cases20
<1% develop neuroinvasive disease, of which 60% develop encephalitis21
High risk patients for neuroinvasive disease: solid organ transplant patients22
Clinical presentation21
Fever: 70-100%
Headache: 50-100%
Encephalopathy: 45-100%
Cranial neuropathies, mostly facial palsy: 20%
Lower motor neuron type lesion: areflexia, hypotonia, preserved sensation
Tremors are not uncommon either
CSF analysis: pleocytosis (>60% of cases lymphocytic predominant), elevated protein and normal glucose13
WNV encephalitis will likely have neuroimaging findings; that is not the case with WNV meningitis
MRI much more sensitive than CT. Most common abnormalities seen involving basal ganglia, brain stem and thalamus1
CSF diagnosis: WNV-specific IgM in CSF23
No established therapy for neuroinvasive disease. Case reports of improvement with IVIG for neuroinvasive disease1
Mortality: 12% in severe neuroinvasive disease. Residual neurological changes such as parkinsonism not uncommon
Approximately 30% of patients reported fatigue symptoms 6 months to 5 years after infection onset24
Viral Meningoencephalitis – Clinical Approach
So you are the house officer encountering a patient with 1-2 weeks of progressively worsening fevers, headaches and severe behavioral changes or depressed mental status: what do you do next?
As a standard work up for likely encephalitis in the United States, CSF studies should include1:
CSF opening pressure
Cell count and differential
Protein and glucose (paired with serum glucose)
Gram stain and bacterial cultures
Initial viral studies to include:
HSV-1/2 PCR;
VZV PCR;
Enterovirus PCR;
WNV IgM serology (if seasonally appropriate);
CSF viral cultures
Imaging in encephalitis: Magnetic resonance imaging (MRI) of the brain is more sensitive than computed tomography (CT)15. Unless contraindicated, all patients with encephalitis should undergo MR imaging.
Temporal lobe and limbic changes → HSV, HHV-619
Hemorrhagic strokes and demyelinating lesions → VZV vasculopathy25
Subependymal enhancement → CMV ventriculitis25
Predominant demyelination → PML (JC virus)
References:
1. Mandell, Douglas and Bennett’s principles and practice of infectious diseases (8th ed. 2015 / Philadelphia, PA : Elsevier) 2. Whitley RJ, and Gnann JW: Viral encephalitis: familiar infections and emerging pathogens. Lancet 2002; 359: pp. 507-513 3. Connolly KJ, and Hammer SM: The acute aseptic meningitis syndrome. Infect Dis Clin North Am 1990; 4: pp. 599-622 4. Gomez B, Mintegi S, Rubio MC, et al: Clinical and analytical characteristics and short-term evolution of enteroviral meningitis in young infants presenting with fever without source. Pediatr Emerg Care 2012; 28: pp. 518-523 5. Rotbart HA: Diagnosis of enteroviral meningitis with the polymerase chain reaction. J Pediatr 1990; 117: pp. 85-89 6. Sawyer MH, Holland D, and Aintablian N: Diagnosis of enteroviral central nervous system infection by polymerase chain reaction during a large community outbreak. Pediatr Infect Dis J 1994; 13: pp. 177-182 7. Ahmed A, Brito F, Goto C, et al: Clinical utility of polymerase chain reaction for diagnosis of enteroviral meningitis in infancy. J Pediatr 1997; 131: pp. 393-397 8. Shalabi M, and Whitley RJ: Recurrent benign lymphocytic meningitis. Clin Infect Dis 2006; 43: pp. 1194-1197 9. Corey L, and Spear PG: Infections with herpes simplex viruses (2). N Engl J Med 1986; 314: pp. 749-757 10. Kupila L, Vuorinen T, Vainionpaa R, et al: Etiology of aseptic meningitis and encephalitis in an adult population. Neurology 2006; 66: pp. 75-80 11. Tan K, Patel S, Gandhi N, et al: Burden of neuroinfectious diseases on the neurology service in a tertiary care center. Neurology 2008; 71: pp. 1160-1166 12. Glaser CA, Gilliam S, Schnurr D, et al: In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. Clin Infect Dis 2003; 36: pp. 731-742 13. Tyler KL: Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret’s. Herpes 2004; 11: pp. 57A-64A 14. Raschilas F, Wolff M, Delatour F, et al: Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 2002; 35: pp. 254-26 15. Domingues RB, Tsanaclis AM, Pannuti CS, et al: Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples. Clin Infect Dis 1997; 25: pp. 86-91 16. Whitley RJ, Alford CA, Hirsch MS, et al: Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 1986; 314: pp. 144-149 17. Lakeman FD, and Whitley RJ: Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 1995; 171: pp. 857-86 18. Whitley RJ, Alford CA, Hirsch MS, et al: Factors indicative of outcome in a comparative trial of acyclovir and vidarabine for biopsy-proven herpes simplex encephalitis. Infection 1987; 15: pp. S3-S8 19. Kramer LD, Li J, and Shi PY: West Nile virus. Lancet Neurol 2007; 6: pp. 171-181 20. Watson JT, Pertel PE, Jones RC, et al: Clinical characteristics and functional outcomes of West Nile Fever. Ann Intern Med 2004; 141: pp. 360-365 21. Sejvar JJ, Haddad MB, Tierney BC, et al: Neurologic manifestations and outcome of West Nile virus infection. JAMA 2003; 290: pp. 511-515 22. Jean CM, Honarmand S, Louie JK, et al: Risk factors for West Nile virus neuroinvasive disease, California, 2005. Emerg Infect Dis 2007; 13: pp. 1918-1920 23. Shi PY, and Wong SJ: Serologic diagnosis of West Nile virus infection. Expert Rev Mol Diagn 2003; 3: pp. 733-741 24. Garcia MN, Hause AM, Walker CM, et al: Evaluation of prolonged fatigue post-West Nile virus infection and association of fatigue with elevated antiviral and proinflammatory cytokines. Viral Immunol 2014; 27: pp. 327-333 25. Gilden DH, Mahalingam R, Cohrs RJ, et al: Herpesvirus infections of the nervous system. Nat Clin Pract Neurol 2007; 3: pp. 82-94
The ATS and IDSA recently released the much-anticipated update to the community-acquired pneumonia (CAP) guidelines. The previous version was published back in 2007 and the new guidelines have included some major changes. Here is a rundown of all those changes that you need to know.
1. Health care associated pneumonia (HCAP) no longer exists
HCAP was an entity created with the 2007 CAP guidelines. It encompassed non-hospital acquired pneumonia in patients who had recent contact with the healthcare system. The recommendation was to treat HCAP with empiric broad-spectrum antibiotic therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PsA). With this strategy however, we were over-treating a lot of people. This study found that while 30% of all patients hospitalized for CAP received empiric anti-MRSA treatment, only 0.7% of all patients had MRSA pneumonia.
In the new guidelines, HCAP no longer exists. Instead, the guidelines emphasize assessment of risk factors for pathogens such as MRSA and PsA.
2.Treatment is now based on severity of the pneumonia rather than the location of the admitted patient
Prior guidelines differentiated antibiotic recommendations based on patient triage to the floor or the intensive care unit. In the new guidelines, treatment recommendations are based on the severity of the pneumonia, based on a list of criteria:
3.Only obtain blood cultures in severe CAP or if risk factors for MRSA and/or PsA are present
The new guidelines focus on cost-effective use of diagnostic tests. Outpatient setting: recommend against any diagnostic testing (except for a chest X-ray) Inpatient non-severe pneumonia: recommend blood cultures and sputum gram stain/culture ONLY if risk factors for MRSA and/or PsA are present Inpatient severe pneumonia: recommend blood cultures, sputum gram stain/culture, Streptococcus pneumoniae urine antigen, and Legionella urine antigen and PCR/culture *Legionella diagnostic tests are also recommended in times of an outbreak
These recommendations are based on literature demonstrating that:
Overall prevalence of true positive blood cultures is 1-9% in patients with CAP3-6
The majority of true positive blood cultures occur in patients with severe CAP6,7
Blood culture results change clinical management in <2% of patients with CAP3,4,6
The rate of blood culture contaminants is similar to the rate of true blood culture positives, resulting in unnecessary antibiotics and extended lengths of stay in the hospital3,4,6
4. Procalcitonin should NOT be used in the diagnosis of CAP
Procalcitonin is not a reliable marker for diagnosis of bacterial infections; it has roughly 65-75% sensitivity for detecting bacterial pneumonia8. Consequently, the risk of not treating bacterial CAP due to a low procalcitonin level can lead to poor outcomes. Although there is data to support use of procalcitonin in determining the duration of antibiotics in CAP9,10, the guidelines recommend use only in situations where duration exceeds the recommended 5-7 days.
The argument from the guideline authors is that there is more literature in support for PSI in accurately predicting mortality rather than the CURB-65 score11-14. However, PSI incorporates data that may not be available in all circumstances, and certainly will not be available to the outpatient clinician who is trying to decide whether to admit a patient or not (such as pH, which can only be obtained from an arterial blood gas). So, although PSI may be recommended for use in the emergency department, the CURB-65 will likely remain in use, especially due to its efficiency in the outpatient setting.
6.Algorithm for CAP antibiotic treatment The meat of the guidelines is the treatment regimens – and there are quite a few changes.
1) Macrolides are no longer recommended as first line therapy in uncomplicated outpatient CAP unless the local streptococcal resistance to azithromycin is <25% (this study shows that most parts of the U.S. have resistance rates >25%).
2) Amoxicillin and doxycycline take the place of macrolides as first line treatment in uncomplicated outpatient CAP.
You may be thinking – “wait, amoxicillin doesn’t even cover atypical pathogens (i.e. Mycoplasma pneumoniae and Legionella pneumophila)!” This is true. But studies have shown that in otherwise-healthy patients, there was no difference in outcomes among those who received amoxicillin vs. an antibiotic that treats atypical organisms16. Exactly why that is remains unclear, but could be because healthy individuals clear the infection on their own or because the majority of these pneumonias are actually due to a virus, so they would improve with or without any antibiotics 5.
3) In hospitalized patients:
Non-severe CAP – only treat empirically for MRSA and/or PsA if the organism has been isolated from the patient’s respiratory tract in the past
Severe CAP – treat empirically for MRSA and/or PsA if the patient has any risk factors for MRSA and/or PsA respiratory infection
7.Treat anaerobes only in cases with suspected or proven lung abscess and/or empyema
Empiric treatment of anaerobes in aspiration pneumonia remains controversial, but the new guidelines recommend only treating anaerobes if there is suspicion for or a proven lung abscess and/or empyema.
8.Continue antibiotics for at least 48 hours in patients who are diagnosed with influenza pneumonia
This recommendation is based off the data that influenza infection predisposes to subsequent bacterial superinfections17 and a patient could have both a viral and a bacterial pneumonia at the same time. The guidelines state that if there is significant clinical improvement in 48 hours and no evidence to suggest a superimposed bacterial pneumonia, antibiotics can be discontinued at that time.
9. Duration of antibiotics is based on clinical improvement (but should be a minimum of 5 days)
Gone are the days of prespecified number of days for antibiotic duration. Instead, monitor the patient for signs of clinical improvement.
If cultures are not growing MRSA and/or PsA, can stop empiric treatment for MRSA and/or PsA.
If clinically improving, stop antibiotics following 48 hours of clinical improvement after a minimum of 5 days. Clinical improvement is determined by resolution of vital sign abnormalities, ability to eat/improved appetite, and normal mentation.
10. Do not use corticosteroids as adjunctive treatment and do not obtain routine follow up chest X-rays
These were not necessarily strategies that I employed prior to the publication of these guidelines, and corticosteroid use in CAP is controversial, but at this time, there is no strong data to support either of these adjunctive management strategies in patients with CAP.
References:
1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Resp Crit Care Med. 2019; 200(7):e45-e67. 2. Self WH, Wunderink RG, Williams DJ, et al. Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes. Clin Infect Dis. 2016; 63(3):300-309. 3. Chalasani NP, Valdecanas MA, Gopal AK, McGowan JE Jr, and Jurado RL. Clinical utility of blood cultures in adult patients with community-acquired pneumonia without defined underlying risks. Chest. 1995; 108(4):932-936. 4. Corbo J, Friedman B, Bijur P, and Gallagher EJ. Limited usefulness of initial blood cultures in community acquired pneumonia. Emerg Med J. 2004; 21(4):446-448. 5. Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. New Eng J Med. 2015. 373:415-427. 6. Lee JH and Kim YH. Predictive factors of true bacteremia and the clinical utility of blood cultures as a prognostic tool in patients with community-onset pneumonia. Medicine (Baltimore). 2016; 95(41):e5058. 7. Waterer GW and Wunderink RG. The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures. Respir Med. 2001; 95(1):78-82. 8. Self WH, Balk RA, Grijalva CG, et al. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis. 2017;65(2):183-190. 9. Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017; 10:CD007498. 10. Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018;18(1):95-107. 11. Aujesky D, Auble TE, Yealy DM, et al. Prospective comparison of three validated prediction rules for prognosis in community-acquired pneumonia. Am J Med. 2005; 118(4):384-392. 12. Marrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, and Feagan BG. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin. JAMA. 2000; 283(6):749-755. 13. Carratala J, Fernandez-Sabe N, Ortega L, et al. Outpatient care compared with hospitalization for community-acquired pneumonia: a randomized trial in low-risk patients. Ann Intern Med. 2005;142(3):165-172. 14. Renaud B, Coma E, Labarere J, et al. Routine use of the Pneumonia Severity Index for guiding the site-of-treatment decision of patients with pneumonia in the emergency department: a multicenter, prospective, observational, controlled cohort study. Clin Infect Dis. 2007;441(1):41-49. 15. Blondeau JM and Theriault N. Application of the Formula for Rational Antimicrobial Therapy (FRAT) to Community-Acquired Pneumonia. J Infect Dis Ther. 2017;5:313. 16. Postma DW, van Werkhoven CH, van Elden LJR, et al. Antibiotic Treatment Strategies for Community-acquired Pneumonia in Adults. New Eng J Med. 2015;372:1312-1323. 17. Metersky ML, Masterton RG, Lode H, File TM Jr, and Babinchak T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis. 2012;16(5):e321-331.
This post is the last in a three-part series covering the management of beta-lactam allergies. Part 1 explained the enormous impact that penicillin allergies have on patient outcomes, while Part 2 discussed the different types of allergic reactions and the potential (or lack thereof) for beta-lactam allergy cross reactivity. This last post will cover the methods used to assess beta-lactam allergies. Let’s jump right in!
There are a variety of strategies that can be used to assess a patient’s beta-lactam allergy, each having their own place in the allergy assessment algorithm. The following will be detailed in this post:
Detailed Patient
Interview
Far and away the most important step in assessing a
patient’s beta-lactam allergy is a detailed patient interview. An allergy
evaluation is recommended by many of the top health organizations in the
country, including the Center for Disease Control and Prevention (CDC),
National Quality Forum, Infectious Diseases Society of America (IDSA), American
Board of Internal Medicine (ABIM), and the American Academy of Allergy, Asthma
& Immunology (AAAAI).1 Just a minute or two of questioning the
patient can yield an entirely different story than the allergy history in the
medical chart. Some common questions I bring up with patients include:
How
many years ago did the reaction occur?
What
type of reaction did you have?
Do
you remember the details of the reaction? Did you have to go to the emergency
room?
How
long after starting the medication did the reaction occur?
How
was the reaction managed?
What
happened when the medication was stopped?
Have
you tolerated other forms of penicillin since the reaction? Have you had Keflex
(cephalexin), Augmentin (amoxicillin/clavulanate), or amoxicillin?
Using
brand names to question patients in this situation is important, as many
patients wouldn’t recognize the jumble of letters that is
amoxicillin/clavulanate
You can develop your own arsenal of questions to ask patients, but the important part is to talk to them. No further strategies are needed if you can rule out the documented allergy just from a 90-second conversation.
Medication History
The other piece that is absolutely necessary before proceeding is looking through the patient’s medication history yourself. If a patient with a documented penicillin allergy received ceftriaxone without issue on an admission last year, you can go ahead and give full-dose ceftriaxone during this admission if needed. The patient interview and medication history review can rule out >50% of documented allergies in my experience. In these situations, you can skip directly to the last section of this post: allergy re-labelling.
Direct Challenge
In patients with a very low probability of allergic
reaction, a beta-lactam antibiotic can usually be given without pause. Situations
where you can rule out an allergy based on patient interview or medication
history can be “challenged” directly. This means giving the full dose of the
preferred antibiotic and monitoring for any adverse effects. Some institutions
also give a direct oral amoxicillin challenge with 250-500 mg of amoxicillin
once prior to the intended beta-lactam initiation. If the patient can tolerate
amoxicillin, any penicillin antibiotic can be given in the future without fear
of experiencing an IgE-mediated reaction.
Graded Challenge
When you are not able to completely rule out an allergic reaction, a graded challenge is often the next logical step in hospitalized patients. Graded challenges are used when there is a low probability of an allergic reaction, but there is still a degree of discomfort giving the entire dose up front. In general, 10% of the full dose is given, the patient is monitored closely for 30 minutes, and then the full dose is given if no issues arise. If the patient tolerates these doses, you can rule out immediate hypersensitivity reactions and document the tolerance in the medical record, which will be discussed at the end of this post.
Snippet of graded challenge guideline table from Brigham & Women’s Hospital
Desensitization
In patients who have confirmed or a high probability of severe IgE-mediated reactions to beta-lactams, but a beta-lactam is necessary for treatment, desensitization can be used. The desensitization procedure usually involves at least 12 doses of escalating concentrations of the required medication. This procedure requires incredibly close monitoring, which at most hospitals requires admission to the intensive care unit for administration. If a patient is able to tolerate desensitization, the patient must then begin regularly scheduled doses of the beta-lactam immediately upon the protocol completion. If doses are missed, the patient must be desensitized again. Desensitization does not rule out the allergy. The patient is still considered allergic to that agent, but can tolerate the medication for the course required in that instance.
Penicillin Skin
Testing
Penicillin (PCN) skin testing has increased in popularity recently due to its relative ease of use and efficacy at ruling out IgE-mediated allergic reactions. In addition to rescue medications that should be handy just in case (diphenhydramine, methylprednisolone, and epinephrine) the skin test consists of 4 elements:
Initially, a percutaneous puncture test is done on the
patient’s forearm with each of the elements and if tolerated, an intradermal
test of each is also performed. The entire process generally takes around 45-60
minutes to complete and offers a negative predictive value for penicillin
allergies of ~99%.2 Debate has surrounded the cost (both time and
materials for the procedure), but multiple studies have now shown penicillin
skin testing to be a cost-saving venture.2-5
Penicillin skin testing seems like a no-brainer, carrying the lowest risk of the procedures discussed thus far and its low overall cost for the health system. But in many institutions, it’s unclear who will perform the testing when allergy consultation is not available. In a 2015 survey of 736 infectious diseases providers, 57% responded saying that they do not have local options for skin testing.6 Does your institution?
The people of Twitter have spoken and it resulted in similar responses, with 62% of respondents not having penicillin skin testing available at their institution. Previous studies have reported on the successes of penicillin skin testing performed by allergists,7-9 & many more antimicrobial stewardship programs,10 infectious diseases fellows/physicians,11 nurses,12 and pharmacists.13,14 If you’ve read this far into the post, you likely are interested in allergy skin testing, so I’d implore you to own the process if your institution doesn’t already have skin testing available! ALK provides some excellent instructional videos on their website to guide you through the testing process. Pharmacists aren’t licensed to perform skin testing in all 50 states, but they are in many of them, which this 2019 article did an admirable job exploring.15
Allergy re-labelling
The last fundamental step in navigating beta-lactam allergies is updating the patient’s allergy label. With all of the previous interventions, the allergy documentation can be further described in the medical record, with desensitization being the only intervention that does not rule out IgE-mediated reactions altogether.
Green denotes interventions that can lead to allergy de-labelling. Red denotes the only intervention that should not lead to de-labelling
In an ideal world, inaccurate allergy labels should be removed from the medical record. Unfortunately, this practice often leads to redocumentation of the allergy at a later admission however.16 Many hospitals have integrated innovative ways to improve this repetitive cycle, as seen via providers’ personal experiences here, here, and here. For those without the tech support for any of this functionality though, the best thing to do is to document, document, document.
Summary
The majority of penicillin allergy labels do not belong to patients with true allergies and these unnecessary labels lead to worse patient outcomes. We should all strive for more accurate and detailed allergy documentation in our patients, which all starts with a patient interview. All of the interventions discussed above can be used to remove/relabel a beta-lactam allergy, with the exception of desensitization.
For those looking to learn more, I highly recommend a recent review published in JAMA that goes into further detail on penicillin allergies.17 Make sure to check out the supplementary material too, it has some super helpful resources, including a full allergy toolkit for penicillin skin testing and oral amoxicillin challenges!
Jones BM, Bland CM. Penicillin skin testing as an antimicrobial stewardship initiative. Am J Health-Syst Pharm. 2017;74:232-7
Mattingly TJ, Meninger S, Heil EL. Penicillin skin testing in methicillin-sensitive staphylococcus aureus bacteremia: A cost-effectiveness analysis. PLoS One. 2019; 14(1):e0210271. doi: 10.1371/journal.pone.0210271
Jones BM, Avramovski N, Concepcion AM, Crosby J, Bland CM. Clinical and Economic Outcomes of Penicillin Skin Testing as an Antimicrobial Stewardship Initiative in a Community Health System. Open Forum Infect Dis. 2019;6(4): ofz109. doi: 10.1093/ofid/ofz109
Rimawi RH, Cook PP, Gooch M, et al. The impact of penicillin skin testing on clinical practice and antimicrobial stewardship. J Hosp Med. 2013;8(6):341-345
Trubiano JA, Beekmann SE, Worth LJ, et al. Improving antimicrobial stewardship by antibiotic allergy delabeling: evaluation of knowledge, attitude, and practices throughout the Emerging Infections Network. Open Forum Infect Dis. 2016; 3(3):ofw153
Macy E, Shu YH. The Effect of Penicillin Allergy Testing on Future Health Care Utilization: A Matched Cohort Study. J Allergy Clin Immunol Pract. 2017;5(3):705-710
Park M, Markus P, Matesic D, Li JT. Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy. Ann Allergy Asthma Immunol. 2006;97(5):681-687
Leis JA, Palmay L, Ho G, et al. Point-of-Care β-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation. Clin Infect Dis. 2017;65(7):1059-1065
Heil EL, Bork JT, Schmalzle SA, et al. Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin Testing Service. Open Forum Infect Dis. 2016;3(3):ofw155
Macy E, Roppe LB, Schatz M. Routine Penicillin Skin Testing in Hospitalized Patients with a History of Penicillin Allergy. Perm J. 2004;8(3):20-24
Chen JR, Tarver SA, Alvarez KS, Tran T, Khan DA. A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients. J Allergy Clin Immunol Pract. 2017;5(3):686-693
Wall GC, Peters L, Leaders CB, Wille JA. Pharmacist-managed service providing penicillin allergy skin tests. Am J Health Syst Pharm. 2004;61(12):1271-1275
Bland CM, Bookstaver PB, Griffith NC, et al. A practical guide for pharmacists to successfully implement penicillin allergy skin testing. Am J Health Syst Pharm. 2019;76(3):136-147
Rimawi RH, Shah KB, Cook PP. Risk of redocumenting penicillin allergy in a cohort of patients with negative penicillin skin tests. J Hosp Med. 2013;8(11):615-618
Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and management of penicillin allergy: a review. JAMA. 2019;321(2):188-199
FOAMid 