Category Archives: MISCELLANEOUS CONCEPTS

How to admit a patient with HIV

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HIV infection has changed dramatically over the last few decades. When we admit patients with HIV to the hospital, the way to approach them can vary widely depending on their immune status and how well their virus is controlled.

In this post, I present a series of steps that you should think about when admitting a patient with HIV to the hospital.

1. ADDRESS privacy concern

Even in 2019, there is significant stigma and discrimination surrounding HIV and those people who live with HIV (PLWH)1. Thus, it’s very important that their HIV status is not disclosed to others without the patient’s permission.

If there are other non-healthcare personnel in the room with the patient (i.e. family members, friends, other patients within hearing distance), do not mention their HIV status until confirmed by patient that it is permissible to discuss it in front of the other individuals.

Options for opening the discussion:

A) “Is it okay if I discuss all your medical conditions in front of these individuals or would you rather talk in private”?

B) Ask everyone else to leave – this will allow you to ask about HIV as well as other potentially sensitive subjects such as sexual history and domestic violence.

C) Proceed with the H&P and ask the patient about their medical history – observe whether they mention HIV or not. If they do not, then do not mention it and come back at a later time to speak to them privately or ask the guests to leave the room for the exam and ask about HIV at that time.

D) If the patient is sharing the room with another patient, then I usually ask about their “viral infection”. Almost all PLWH will know what you are referring to. Then I wait to see if the patient mentions the word “HIV” or “AIDS” themselves – if they do, then I take that as a signal that it is permissible to talk about it openly (in that particular setting only) and if they do not, then I proceed with as much information as I can elicit without using the word “HIV” or making it obvious that I am discussing “HIV”.

2. ASSESS the immune status

The immune status is determined by their CD4+ count/percentage. However, usually you don’t know their current CD4+ count at the time of admission. What to do?

a) If they have been to your hospital/system before, check their chart for prior CD4+ counts. That should give you a general idea of their immune status.
–if patient is taking antiretroviral therapy (ART), current CD4+ is likely the same or improved
–if patient stopped/not taking ART, current CD4+ is likely the same or worsened

b) Ask the patient! Most of the patients know their CD4+ counts or at least know if its low or high

c) Call the patient’s HIV provider

d) Rough estimate2:
-Absolute lymphocyte count >2000cells/mm3 –> CD4+ cells >200cells/mm3
-Absolute lymphocyte count <1000cells/mm3 –> CD4+ cells <200cells/mm3

*Also, please keep in mind that CD4+ counts are affected by changes in total white blood cell counts, so in an acute illness, the CD4+ percentage (which is not affected by the WBC count) is a more stable marker of immune status. Generally, a CD4+ count obtained during a routine office visit will be more accurate of their immune status than one obtained during a hospital admission.3

3. DEVELOP differential for their concern/symptoms based on immune status

A. If CD4+ >500cells/mm3, then their immune system is intact and there is low likelihood of opportunistic infections.

B. If CD4+ 200-500cells/mm3, then their immune system remains compromised and still susceptible to infections. Also, there is potential that since the last CD4+ count, they have stopped taking their medications and could now be below 200cells/mm3. Consider opportunistic infections, but should be lower on the differential.  

C. If CD4+ <200cells/mm3, opportunistic infections NEED to be on your differential. Treat the patient as an immunocompromised individual and tailor empiric therapy as appropriate.4,5,6

*However, common things being common — a patient with HIV is still at risk for other non-opportunistic infections such as bacterial pneumonia and hospital-acquired infections.

Created by David Serota (@serotavirus)

4. FIND OUT if they are currently taking ART and which ones?

A.If they are not taking ART, then do not start ART on admission until discussed with an HIV provider

B.If patient has ART prescribed but has not been taking them, do not restart the medications on admission until discussed with the patient’s HIV provider. Starts and stops in the medications can promote viral resistance to the drugs.

C.If patient is on ART, continue the ART (unless clear obvious reason not to, i.e. allergy). Find out from patient, family member (who is aware of status), HIV provider/PCP, pharmacy, or medical record what treatment they are on – often patients will be on a combination pill that may not be available in your hospital. In these cases, look up the individual medications in the combination pill and prescribe them all separately.7

5. RUN a drug interaction check when starting ANY new medications

Failure to do this can cause increased metabolism of the HIV medications leading to resistance, or cause increased/decreased metabolism of the other medications leading to inadequate treatment or toxicity. Use this website to check for drug-drug interactions.

6. DETERMINE most recent HIV viral load

–if patient has been on ART regularly, then viral load will likely be undetectable
–if patient has not been on ART regularly, then viral load will likely be detectable 

7. TAKE a sexual history

– assess risk for other STDs
– assess risk for HIV transmission to sexual partners
– educate on U=U and PrEP

8. ASK them about their experience and history of HIV, once you to get to know them.

You will learn a lot that medical books will never be able to teach you.

Was this helpful? Did I miss something? Let me know in the comments!

References
1. Turan B, Budhwani H, Fazeli PL, Browning WR, Raper JL, Mugavero MJ, et al. How Does Stigma Affect People Living with HIV? The Mediating Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community Stigma on Health and Psychosocial Outcomes. AIDS Beh. 2017; 21(1):283-291. 10.1007/s10461-016-1451-5.
2. Shapiro NI, Karras DJ, Leech SH, and Heilpern KL. Absolute lymphocyte count as a predictor of CD4 count. Ann Emerg Med. 1998; 32(3 Pt 1):323-328. 10.1016/s0196-0644(98)70008-3
3.Feeney C, Bryzman S, Kong L, Brazil H, Deutsch R, and Fritz LC. T-lymphocyte subsets in acute illness. Crit Care Med. 1995; 23(10):1680-1685. 10.1097/00003246-199510000-00012
4. Taylor JM, Sy JP, Visccher B, and Giorgi JV. CD4+ T-cell number at the time of acquired immunodeficiency syndrome. Am J Epidemiol. 1995; 141(7): 645-651. 10.1093/oxfordjournals.aje.a117480
5. Hanson DL, Chu SY, Farizo KM, and Ward JW. Distribution of CD4+ T lymphocytes at diagnosis of acquired immunodeficiency syndrome-defining and other human immunodeficiency virus-related illnesses. The Adult and Adolescent Spectrum of HIV Disease Project Group. Arch Intern Med. 1995; 155(14):1537-1542.
6. Mocroft A, Furrer HJ, Miro JM, Reiss P, Mussini C, Kirk O, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/μL in the post-combination antiretroviral therapy era. Clin Infect Dis. 2013; 57(7):1038-1047. 10.1093/cid/cit423
7. Management of the Treatment-Experienced Patient. AIDSInfo. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. U.S. Department of Health and Human Services. Site updated August 29, 2019. Retrieved August 29, 2019. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/18/discontinuation-or-interruption-of-antiretroviral-therapy 10.1097/00003246-199510000-00012

Zoonotic infections

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When I was an aspiring Infectious Disease fellow, I marveled at how the ID doctors would come up with diseases that no one else had thought of. How did they do that?

They obtain a detailed patient history. (It’s the ID doctors equivalent of a procedure!)

Contact or exposure to certain animals are associated with certain diseases.

These are examples of some of the questions to ask to ascertain whether your patient has been in contact with specific animals:
– Do you have any pets? Do you have frequent contact with anyone else’s pets?
– Do you have contact with any farm or wild animals?
– What do you do for work (farmer, veterinarian, kennel worker, biologists, etc)?
– What do you do for fun (hunting, fishing, cave explorer, raising chickens, etc)?

I’ve created an easy graphic to give you an idea of some diseases that are associated with different animals your patients might encounter. This is to help you quickly look up which infections you should consider in your differential if your patient reports an exposure to one of these animals.

*This list does not include ALL pathogens. This is just a list of the most common plus others to think about in certain situations. In places outside of North America, this list may look
different.
**This is not intended to take the place of a formal infectious disease consult.
***Use this chart in the context of the clinical presentation. It does not mean you should test for all these infections in every patient, but rather gives you a quick reminder to consider them in your differential.

Was this helpful? Did I miss something? Tell me what you’re thinking with a comment!

References:

1. Centers for Disease Control and Prevention. Healthy Pets Healthy People. http://www.cdc.gov/healthypets/pets/cats.html (Accessed on Feb 23, 2019).
2. Day MJ. Pet-Related Infections. Am Fam Physician. 2016; 94(10):794-802.
3. Goldstein EJC and Abrahamian FM. Diseases Transmitted by Cats. Microbiol Spectr. 2015; 3(5).
4. Chomel BB. Emerging and Re-emerging Zoonoses of Dogs and Cats. Animals (Basel). 2014; 4(3):434-445.
5. Dyer JL, Yager P, Orciari L et al. Rabies surveillance in the United States during 2013. J Am Vet Med Assoc. 2014; 245(10):1111-1123.
6. Boseret G, Losson B, Mainil JG, et al. Zoonoses in pet birds: review and perspectives. Vet Res. 2013; 44(1): 36.
7. Kwon-Chung KJ, Fraser JA, Doering TL, et al. Cryptococcus neoformans and Cryptococcus gattii, the Etiologic Agents of Cryptococcosis. Cold Spring Harb Perspect Med. 2014; 4(7):a019760.
8. National Association of State Public Health Veterinarians, Inc. (NASPHV), Centers for Disease Control and Prevention (CDC). Compendium of measures to prevent disease associated with animals in public settings, 2011: National Association of State Public Health Veterinarians, Inc. MMWR Recomm Rep 2011; 60:1.
9. Kotton CN. Zoonoses from pets other than dogs and cats. UpToDate. Published Jan 2019. Accessed on Feb 23, 2019.

Non-infectious causes of fever

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This post is co-written with the guest writer Ahmed Abdul Azim, MD.

Not all fevers are caused by infections.

It is important that every patient presenting with fever is evaluated for an infection….. but what do you do when no infection is found?

thermometer2.png

Why are non-infectious causes of fever important to know?

If a patient is treated for a presumed infectious fever when they don’t have an infection:

  • there is a delay in identifying the correct diagnosis
  • they are exposed to prolonged courses of unnecessary antibiotics

 

Definition of fever

Fever = 38.3°C (101°F) or above1

Pyrogenic agents = substances that can induce a fever.
a) Exogenous pyrogens – external substances that activate our immune system to induce a fever (ex. microbial toxins)
b) Endogenous pyrogens – cytokines that induce fever in our body
(ex. IL-1, IL-6, tumor necrosis factor, IFN-α, ciliary neutrotrophic factor, and likely others)

 

Non-infectious causes of fever:

1. Rheumatologic/autoimmune – activation of immune system that stimulates the production of pyrogenic cytokines
– the cause of ~30% of fevers of unknown origin

a) Adult-onset Still’s disease – younger patients, daily fevers >39°C, rash, arthritis
b) Giant cell arteritis – older patients, vision changes, jaw claudication
c) Others – polyarteritis nodosa, Takayasu’s arteritis, granulomatosis with polyangiitis, etc.

2. Malignancy – tumor cells release pyrogenic cytokines

a) Lymphomas and leukemias – most common; seen in high burden of disease
b) Myelodysplastic syndromes
c) Renal cell carcinoma – ~20% of cases present with fevers
d) Hepatocellular carcinoma or liver metastases
e) Atrial myxomas

3. Drug-induced fever – 3-5% of drug-related adverse reaction in hospitalized patients include fevers6
– typically occurs 7-10 days after drug initiation, but can be as soon as 24 hours and as far away as a few years from drug initiation7
– patients typically appear “inappropriately” well
– eosinophilia (>500/mm3) occurs in 20-25% of patients with drug-induced fevers10
– PATHOPHYSIOLOGY:

a) Hypersensitivity reaction – due to activation of T cell immune response by drug, its metabolite, or the formation of an immune complex
– typically occurs ~3-10 days after drug exposure
– typically resolves 72-96 hours after discontinuation of drug (but can be more delayed)
– symptoms will recur immediately upon rechallenge

1) Antimicrobials – most common cause of drug fever
– minocycline, beta-lactams (penicillin-based > cephalosporins10), sulfonamides, nitrofurantoin
2) Anticonvulsants – carbamazepine, phenytoin, phenobarbital
3) Allopurinol
4) Others

– DRESS syndrome – a severe type of drug hypersensitivity reaction
(typically occurs 2-6 weeks after drug exposure)

b) Administration-related – typically last <48 hours

1) Vaccines – stimulation of the immune system → release of pyrogenic cytokines
2) Amphotericin B – exogenous pyrogenic agents

c) Pharmacologic action of the drug – transient fever; self-resolving

1) Anti-neoplastic agents – cause severe and rapid tumor cell lysis → release of endogenous pyrogenic agents → inflammatory response (fever)
2) Antimicrobials – cause rapid death of microbes → microbial cell lysis → release of exogenous pyrogenic substances → inflammatory response (fever)
–  ex. Jarisch-Herxeimer reaction in syphilis treatment with penicillin

d) Altered thermoregulation – disturbance of the central hypothalamic thermoregulation function and/or increased heat production

1) Exogenous thyroid hormone
2) Anticholinergic drugs
3) Sympathomimetic agents

cold winter tablet hot

e) Idiosyncratic drug reactions

1) Serotonin syndromes – linezolid, SSRIs
2) Neuroleptic malignant syndrome
– anti-psychotics, dopamine antagonists
3) Malignant hyperthermia syndrome
– inhaled anaesthetics, paralytic agents
4) G-6-PD deficiency – dapsone, primaquine, nitrofurantoin, etc.

4. Other causes

1) Transfusion of blood cells – RBCs, platelets, WBCs
2) Central fevers – fevers due to central thermodysregulation due to CNS damage
– more common with CNS hemorrhage and brain tumors11
– fever onset within 72 hours of sustaining CNS hemorrhage
3) Thromboembolism – typically <102°F
4) Endocrine – thyroid storm; adrenal insufficiency
5) Pulmonary – ARDS, aspiration pneumonitis, cryptogenic organizing pneumonia
6) Intra-abdominal – acute pancreatitis, cholecystitis, mesenteric ischemia

*Non-infectious causes of fevers are diagnoses of exclusion. A patient MUST have an appropriate workup for infectious causes prior to considering any of the non-infectious causes of fever.

*A lot of these diagnoses need to be made based on clinical symptoms and signs and requires a high degree of suspicion.

*Fever is a sign of an underlying inflammatory process.
DO NOT TREAT THE FEVER — TREAT THE UNDERLYING CAUSE.

 

References:

  1. O’Grady NP, Barie PS, Bartlett JG, et al. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med. 2008; 36(4):1330-1349.
  2. Dekker AR, Verheij TJ, and van der Velden AW. Inappropriate Antibiotic Prescription for Respiratory Tract Indications: Most Prominent in Adult Patients. Family Practice. 2015; 32(4):401-407.
  3. Mackowiak PA, Wasserman SS, and Levine MM. A Critical Appraisal of 98.6°F, the Upper Limit of the Normal Body Temperature, and Other Legacies of Carl Reinhold August Wunderlich. JAMA. 1992; 268(12):1578-1580.
  4. Obermeyer Z, Samra JK, and Mullainathan S. Individual Differences in Normal Body Temperature: Longitudinal Big Data Analysis of Patient Records. BMJ. 2017; 359:j5468.
  5. Westbrook A, Pettila V, Nichol A, et al. Transfusion Practice and Guidelines in Australian and New Zealand Intensive Care Units. Intensive Care Med. 2010; 36(7):1138-1146.
  6. Lipsky, BA and Hirschmann JV. Drug Fever. JAMA. 1981; 245(8):851-854.
  7. Mackowiak, PA. Southwestern Internal Medicine Conference: Drug Fever: Mechanisms, Maxims and Misconceptions. Am J Med Sci. 1987; 294(4):275-286.
  8. Patel, RA and Gallagher JC. Drug fever. Pharmacotherapy. 2010; 30(1):57-69.
  9. Johnson DH and Cunha BA. Drug fever. Infect Dis Clin North Am. 1996; 10(1):85-91.
  10. Oizumi K, Onuma K, Watanabe A, et al. Clinical Study of Drug Fever Induced by Parenteral Administration of Antibiotics. Tohoku J Exp Med. 1989; 159(1): 45-56.
  11. Hocker SE, Tian L, Li G, et al. Indicators of Central Fever in the Neurologic Intensive Care Unit. JAMA Neurology. 2013; 70(12):1499-1504.
  12. Porat R and Dinarello CA. Pathophysiology and treatment of fever in adults. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/pathophysiology-and-treatment-of-fever-in-adults]. Accessed Dec 26, 2018.

IDWeek 2018 Review

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Dolores Park SF
Mission Dolores Park in San Francisco – photo courtesy of Ahmed Abdul Azim @triplea87

 

During the first week of October, the Infectious Diseases Society of America (IDSA) hosted its’ annual Infectious Diseases conference (IDWeek) in San Francisco, California.

There are a variety of reviews of the conference on the internet (the most famous being the Mini Really Rapid Review by Dr. Paul Sax) but I want to highlight the studies that are pertinent to physicians in other specialties outside of ID.

 

  • Two major studies highlighted the ongoing pressures and scope for over-prescription of antibiotics and need for antimicrobial stewardship
    In one study, 66.1% of patients were prescribed antibiotics for respiratory tract infections and antibiotic prescribing was associated with higher patient satisfaction. Given that most respiratory tract infections are viral, 66% is a lot!
    Another study showed that 20% of antibiotics are prescribed without an in-person visit. Of all the 509,534 antibiotic prescriptions, 46% were not associated with an infection-related diagnosis. This highlights the need for better provider and patient education in antibiotic stewardship.

 

 

 

 

 

 

 

 

 

 

  • IV drug use may be an independent risk factor for candidemia.
    This study showed an increasing incidence of candidemia and higher numbers of patients with candidemia who are persons who inject drugs without other risk factors. Something to keep in mind when you see patients who inject drugs in your hospital.

 

And for those of you in San Francisco, watch out for these microbes:

 

It’s impossible to cover everything so if you attended IDWeek and have other studies to suggest to everyone, let us know in the comments.

5 things that ID fellows wish you knew

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3rdtimeisthe charm

1. Yeast in the sputum does not always need treatment.

We often see yeast pop up in sputum cultures and BAL cultures in ICU patients. However, yeast in hospitalized patients is typically Candida species, which are NOT typical pulmonary pathogens. Candida pneumonia is rare. In a recent study that looked at how often yeast isolated from sputum/BAL culture in ICU patients truly are reflective of Candida pneumonia, they found that 5/701 samples were consistent with Candida pneumonia (0.7%).  3/5 patients had severe gastric contents aspiration and 4/5 were immunocompromised.1

What does this mean? Unless the patient recently had significant aspiration or is immunocompromised, Candida spp. in the sputum is unlikely to be a true pathogen.

Other potential yeasts can include Cryptococcus spp., Histoplasma capsulatum, Blastomycosis spp., Coccidioides spp., and Paracoccidioides spp. These can represent true clinical infections. Treatment for these infections is different from Candida spp. and risk should be assessed given the patient’s clinical context.

 

2. It’s all about “source control”.

This means that if the area of infection can be physically removed or debrided, it should be done to optimize the chance of cure. This can also help increase diagnostic yield for targeted antibiotic therapy. Examples:

  • If there is an abscess, it should be drained, if possible.
  • If there is an infected foreign body, it should be removed, if possible.
  • If there is infected bone, it should be debrided/removed, if possible.

The STOP-IT trial in 2015 showed that in patients with intra-abdominal abscesses who received adequate source control (drainage of abscess or surgical resection), 3-5 days of antibiotics post-source control was non-inferior to 8-10 days of antibiotics after source control.2

There are obviously times when source control is not possible, too risky, or may cause more harm than benefit. However, anytime a patient has an infection, source control should be considered in the initial management strategy.

 

3. Do not treat asymptomatic bacteriuria and do not send urine cultures on asymptomatic patients.

  • The urogenital tract is not a sterile area and bacteria are often found that are not causing any symptoms or harm to the patient.
  • Antibiotics that are started for asymptomatic bacteriuria can cause harm.
  • If a patient has a urinary catheter, replace urinary catheter and resend a urine culture.
  • Pyuria in asymptomatic bacteriuria does not require treatment3.

 

The 2 times to treat asymptomatic bacteriuria:

  1. Pregnant patients
  2. Patients who are about to undergo a urologic procedure

 

A Cochrane review published in 2015 evaluated 9 randomized-controlled-trials (and a total of 1614 non-pregnant adults) who looked at antibiotic treatment vs. placebo for asymptomatic bacteriuria, and demonstrated that there was no difference in development of symptomatic urinary tract infections, UTI complications, or death between the two groups. The treatment group had a 3.77 increased risk of antibiotic side effects.4

 

4. Beta-D-glucan results need to be taken in the context of the patient’s clinical picture.

Not all fungal infections cause elevated beta-D-glucan and not all elevated beta-D-glucan levels indicate a fungal infection.

Initial studies that looked at beta-D-glucan test characteristics were done in immunocompromised patients. In that group, the test performed well, with sensitivity ranging 64-95% and specificity ranging from 92-95% (variation depending on prevalence and test level cutoff for positivity).5-7

However, in the non-immunocompromised population in the intensive care units, the test has not shown to have the same specificity. The sensitivity remains high in the 80%-90% range while specificity drops as low as 38% in non-neutropenic patients with known candida colonization.8-10

5. Send a GeneXpert© NAAT test with the first AFB smear and remember that there is no such thing as a “TB rule out”.

The current CDC/IDSA guidelines in evaluation of active pulmonary tuberculosis is to:

  • obtain 3 sputum AFB smears/cultures at least 8-24 hours apart.11
  • ideally obtain at least one smear as an early morning sample (highest concentration of mycobacteria at that time).11
  • send a GeneXpert© nucleic acid amplification test (NAAT) on the 1st sputum specimen.11
    ⇒ This test can detect tuberculosis genes as well as detect rifampin susceptibility and usually comes back quickly.
  • A bronchial (BAL) specimen can count as one sputum sample.11
  • In the US from 2011-2013, only 46% of patients with TB had a positive AFB smear.
    ⇒ Three negative sputum AFB smears does not “rule out” TB. The patient can still have TB, but the probability of TB is lower and they are less likely to be infectious if all three smears are negative.11,12,13

 

 

References:

  1. Schnabel RM, Linssen, CF, Guion CF, van Mook WN, and Bergmans DC. Candida pneumonia in Intensive Care Unit? OFID. 2014;1(1) ofu026. doi:https://doi.org/10.1093/ofid/ofu026
  2. Sawyer RG, Claridge JA, Nathens AB, et al. Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection. NEJM. 2015; 372:1996-2005. doi:10.1056/NEJMoa1411162
  3. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. CID. 2005; 40: 643-654.
  4. Trestioreanu, AZ, Lador A, Sauerbrun-Cutler M, and Leibovici, L. Antibiotics for asymptomatic bacteriuria. The Cochrane Database of Systematic Reviews. 2015. doi:10.1002/14651858.CD009534.pub2
  5. Odabasi Z, Mattiuzzi G, Estey E, et al. β- d -Glucan as a Diagnostic Adjunct for Invasive Fungal Infections: Validation, Cutoff Development, and Performance in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Clin Infect Dis. 2004; 2(15):199-205. doi:https://doi.org/10.1086/421944
  6. Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter Clinical Evaluation of the (1→3) β-D-Glucan Assay as an Aid to Diagnosis of Fungal Infections in Humans. Clin Infect Dis. 2005; 41(5): 654-659. doi:https://doi.org/10.1086/432470
  7. Obayashi T, Negishi K, Suzuki T, and Funata N. Reappraisal of the serum (1–>3)-beta-D-glucan assay for the diagnosis of invasive fungal infections–a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46(12):1864-70. doi:10.1086/588295
  8. Mohr JF, Sims C, Paetznick V, et al. Prospective survey of (1à3)-beta-D-glucan and its relationshop to invasive candidiasis in the surgical intensive care unit setting. J Clin Microbio. 2011; 49(10):58-61. doi:10.1128/JCM.01240-10
  9. Liew YX, Teo J, Ai-Ling Too I, et al. Candida Surveillance in Surgical Intensive Care Unit (SICU) in a Tertiary Institution. BMC Infect Dis. 2015; 15(256):1-8. doi:10.1186/s12879-015-0997-6
  10. Lo Cascio G, Koncan R, Stringari G, et al. Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit. Eur J Clin Microbiol Infect Dis. 2015; 34(2):357-365. doi:10.1007/s10096-014-2239-z
  11. Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL et al. Official American Thoracic Society/Infectious Disease Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. 2017; 64(2):111-115. doi: 10.1093/cid/ciw778
  12. Mase S, Ramsay A, Ng N, Henry M, Hopewell PC, Cunningham J, Urbanczik R, Perkins M, Aziz MA, Pai M. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis. 2007;11(5):485-95. PMID:17439669
  13. CDC. Reported Tuberculosis in the United States, 2013. Atlanta, GA: U.S. Department of Health and Human Services, CDC, October 2014.