A Candida Comeback?

Hello again everyone! And special thanks to the readers who read, commented, shared, and reached out to me from my last post “A Serious Aside,” talking about physician burnout and health worker suicide. Numerous people had so much to say in support of this topic—and it’s well deserved—sharing their personal stories and relating their own connects, so I truly appreciate it.

This time, how about something different? In the past few months, I’ve been working through my clinical rotations at a major community hospital in New York City, in the Bronx. A CDC-sponsored screensaver image keeps appearing at terminals throughout floors, services, and clinics; and it directly addresses healthcare professionals to monitor hygiene practices to eliminate Candida infections. I’ll have to admit—innocuous stuff—I’ve been seeing health-message PSA-like screensavers at work for years, about a myriad of topics. Who hasn’t seen those? “Keep beds out of the hallways,” “Protect you and your patients from MRSA,” “Make sure lab requisitions are filled out properly…” the list is endless. But having seen my aforementioned screensaver about Candida one too many times, I had to find out what this was about. You might have thought that, since I spent time working in an HIV clinic, this was a simple PSA for those patients otherwise immunocompromised. Right? Nope.

This particular PSA from the CDC warns about Candida auris, a true blue (or pinkish gold, rather) member of everyone’s favorite budding, germ-tube positive, yeast family. C. auris has been in literature for roughly the past decade. Having etiologic origins in southeast Asia and spreading west through the Middle-East, all throughout Africa, and even the UK, this bug has caught the eyes of epidemiologists around the world. Two years ago, the CDC1 and Public health England2 issued warnings about this pathogen, its multi-drug resistance, and its virulence in healthcare-associated infections. Last fall, the NY State Department of Health published their official update for guiding clinicians and laboratory staff.3 In this report, they discussed infection control, prevention, and detection limitations.

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Image 1. CDC screensaver on hospital computers. Due to increased incidence of reported cases, epidemiologic data suggest prevention measures would benefit patients. C. auris is associated with healthcare-related infections and can live in the environment for an extended period of time.
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Image 2. NY State Department of Health, Report on C. auris. Informing clinicans and laboratory staff about epidemiology, prevention, detection in the laboratory, and associated implications of limitations and multidrug resistance.

So what’s so scary about C. auris? The two most challenging features of this emerging pathogen are its multi-drug resistance and its relatively difficult identification.

This yeast has been shown to show resistance to many antifungal/antimicrobial agents including fluconazole, voriconazole, amphotericin-B, echinocandins, and even flucytosine. Even more concerning is that nearly half of the C. auris strains collected in research done in Asia, Africa, and South America demonstrated multi-drug resistance patterns to two or more combination therapies. These are most of our first-line standard of care therapies for invasive candidiasis in patients!

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Image 3. UpToDate recommendations summary for candidemia and invasive candida infections.

There are various other recommendations regarding therapies to C. auris specifically, as its potential for resistance are known, but infection control along with empiric therapy seem to be the current standard.

The major risk factors for C. auris infections include the relative status of individual patients: intensive care, acute renal failure, immunocompromised status, localized or systemic infections, and colonization. Simply being hospitalized is an associated risk. On my current service of patients I’m part of a nephrology/medicine team. There are several chronic infection, ESRD, immunocompromised, or otherwise applicable patients to these risk stratifications. No wonder we’ve got those screensavers!

Concerns for identifying C. auris take us back to the lab. Detecting this bug is not as simple as a couple microscopic morphologies and a yeast API strip—sorry to my old mycology professors. C. auris based on chemical tests like these can produce confounding results. Even VITEK identification (unless you’re running Vitek 2 with Biomerieux software) or culture growth can yield non-specifics like C. haemulonii or Saccharomyces cerevisiae. C. auris has a very high salt and temperature tolerance, and with no particular morphologic identifiable features, it remains a challenging identification. It can be grown on dulcitol agar or CHROMagar, but you do not get clear results. What’s the way to get the ID then? Ultimately MALDI-TOF, PCR, and molecular testing is the answer. There are already available C. auris sequences you can obtain for in-house validation if you’re using MALDI already. And when it comes to susceptibility, fear not: as far as I’ve been able to read E-Tests still work.

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Image 4. Definitely not a definitive CHROMagar result.

I was very impressed with MALDI when I was working in Chicago, and a community hospital I was with just finished validating when I left for medical school. I am glad to see it again with this emergent pathogen, and it definitely demonstrates the next wave of instrumentation. Extremely rapid and very accurate.

The variable drug susceptibility, virulence, and ability to thrive in the environment actively threaten those with long inpatient stays. This microorganism is treated with standard precautions and infection control measures. Currently NY leads the nation by far in purported cases of C. auris. So … please wash your hands. A lot. I know I am.

Thanks! See you next time!

References

  1. Centers for Disease Control and Prevention. Clinical Alert to U.S. Healthcare Facilities – Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html
  2. Public Health England. Candida auris identified in England. https://www.gov.uk/government/publications/candida-auris-emergence-in-england/candida-auris-identified-in-england
  3. NY State Department of Health https://www.health.ny.gov/diseases/communicable/c_auris/docs/c_auris_update_for_lab_staff.pdf

 

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Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student at the American University of the Caribbean and actively involved with local public health.

Microbiology Case Study: A 59 Year Old Female with Fevers, Weakness, and Altered Mental Status

Case History

A 59 year old African American female presented to the emergency department with fevers, weakness, fatigue and altered mental status. Her past medical history was significant for hypertension, diabetes mellitus (type 2) with end stage renal disease and a recent cerebrovascular accident the month prior. Her surgical history included a mitral valve repair surgery three years ago and a renal transplant two years ago. Current medications included prednisone, mycophenolate and tacrolimus immunosuppressive agents. Physical examination was unremarkable except for a temperature of 101°F and she was oriented to person, place and time. Pertinent labs included a WBC count of 13.2 TH/cm2, microcytic anemia, and a creatinine of 1.51 mg/dL. Due to previous cardiac surgery, a transesophageal echocardiograph (TEE) was performed and showed a large vegetation (1.6 x 1.5 cm) on the mitral valve.  A diagnosis of endocarditis was made and the patient was started on broad-spectrum antibiotics & taken to surgery for a mitral valve replacement. Multiple blood cultures were negative to this point. Portions of the mitral valve were submitted to surgical pathology and the microbiology laboratory for bacterial, fungal and AFB cultures.

Laboratory identification

Surgical pathology received an aggregate of tan-yellow, fibrous tissue fragments (3.1 x 1.5 x 1.1 cm). Histologic assessment showed a confluent mass containing abundant narrow, septate hyphae consistent with a fungal infection (Image 1). No definitive pigment was identified. Grocott’s methenamine silver (GMS) stain also highlighted the narrow hyphae with numerous septations (Image 2). In the microbiology laboratory, a darkly pigmented mold grew after 5 days of incubation on Sabouraud dextrose agar (Image 3). Lactophenol cotton blue prep showed pigmented, curved conidia with 2-3 transverse septations consistent with Curvularia spp (Image 4). All blood cultures were finalized as no growth after 5 days. Fungitell was found to be greater than 500 pg/ml and Aspergillus galactomannan was negative (<0.5).

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Image 1. Sections of mitral valve tissue showed a confluent mass of abundant hyphal elements (H&E, 4x).
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Image 2. Special stains of the fungal mass highlighted narrow hyphae with numerous septations and acute angle branching (GMS, 4x).
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Image 3. A darkly pigmented mold grew of Sabouraud dextrose agar after 5 days of incubation at 25°C.
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Image 4. Many pigmented, curved conidia with multiple transverse septations were seen (lactophenol cotton blue prep, low power).

Discussion

Curvularia spp. belong to a heterogeneous group of dematiaceous or black molds. The presence of pigment in this category of molds is due to melanin in the hyphae. Dematiaceous molds are ubiquitous in nature and can occasionally cause human infections.  These molds have a characteristic dark appearance on fungal media that is often dark gray, brown or black in color. In addition, when the reverse of the plate or slant is examined, the under surface is also pigmented. Based on their growth rate, the dematiaceous fungi are divided into the fast growers, such as Curvularia, Bipolaris and Alternaria spp., which are mature in 5-7 days. The second group is slow growers that take between 7-25 days to fully mature. Examples of slow growers include Phialophora, Exophila/Wangiella, Cladosporium, Fonsecaea and Rhinocladiella spp.

Most commonly, dematiaceous molds infections usually present as phaeophyphomycosis, chromoblastomycosis or mycetomas. These three entities are cutaneous or subcutaneous mycoses that are obtained by traumatic implantation but vary from one another based on clinical features and histologic features of the mold in tissues. They are most frequently cause infection in male agricultural workers in rural areas of tropical or subtropical climates.  These infections are indolent in nature but can lead to significant morbidity over time, as they are difficult to treat effectively.

In addition to the above superficial infections, Curvularia spp. has also be known to cause keratitis, sinusitis and wound infections. In immunosuppressed individuals, disseminated infections with spread to the lungs and brain have been documented. Endocarditis due to Curvularia spp. is quite rare with very few cases previously reported in the literature. On those documented, Curvularia spp. infections tend to have a predilection for prosthetic heart valves or occur after cardiac surgery. Diagnosis of infective endocarditis is difficult as symptoms are indolent and blood cultures do not have a high yield. Therefore, culture of the vegetation may be the only way to make a diagnosis.

In the microbiology laboratory, Curvularia spp. will grow on routine fungal media as a darkly pigmented mold in a relatively short time. On lactophenol cotton blue prep, Curvularia spp. produce large conidia that usually contain 4 cells that are divided by transverse septations. The conidia take on a curved appearance due to swelling of the subterminal cell, which is often the largest and most deeply pigmented. If identification is necessary beyond the genus level, panfungal PCR assays followed by sequencing of ribosomal genes may be useful in providing a species level diagnosis from fresh or paraffin embedded tissue.

For localized infections, surgical treatment alone may be adequate in some cases.  In infections that are extensive or if there is dissemination, treatment with newer triazoles, such as posaconazole or voriconazole, have shown a broad spectrum of activity against dematiceous molds. Amphotericin B is also another effective option. While susceptibility testing can be performed on clinically significant Curvularia spp. infections, interpretative breakpoints have not been defined and clinical correlation is lacking.

In the case of our patient, she remained on a ventilator following surgery and with the identification of mold on histology, she was started on micafungin. She was switched to amphotericin B after the mold was classified as Curvularia spp. Her condition did not improve despite therapy and she died 3 weeks after surgery.

 

-Azniv Azar, MD, is a fourth year anatomical and clinical pathology resident at the University of Mississippi Medical Center.

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-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. She is the director of the Microbiology and Serology Laboratories. Her interests include infectious disease histology, process and quality improvement, and resident education.

Microbiology Case Study: A 52 Year Old Man with End Stage Renal Disease

Case History

A 52-year-old man with multiple medical issues including a history of end stage renal disease on hemodialysis, chronic pancreatitis status post distal pancreatectomy, intravenous drug use through dialysis catheter, and multiple types of bacteremia presented with chills and abdominal pain. Labs on admission included a white blood cell count of 28.64 k/cmm, hemoglobin 8.8 g/dL, and platelets 581 K. He was diagnosed with a pancreatitis flare and admitted for pain management, with further labs drawn. After one day, he felt much better and was discharged with a pending blood culture to follow up on. At 61 hours, one bottle flagged positive with yeast seen on gram stain.

Laboratory findings

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Image 1: potato flake agar with creamy tan-white colonies.
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Image 2: calcofluor white fluorescent stain showing round yeast forms.

The organism was identified as Cryptococcus laurentii via MALDI-ToF MS. A follow-up fungal culture was negative, however, repeat blood culture grew Stenotrophomonas maltophilia. His tunneled catheter was removed, and two days later the patient required urgent interventional radiology access for dialysis. He completed a two-week course of ceftazidime and was discharged. 

Discussion 

Cryptococcus laurentii is a very rare fungal pathogen. It is a psychrophilic organism, growing ideally at 15 °C, and is the most common yeast found in tundra.1 Major reservoirs include soil, food, and pigeon excrement.2 C. laurentii usually causes infection in immunocompromised hosts, although rare incidents of infection in immunocompetent patients have been reported. Reported manifestations have included fungemia, meningitis, peritonitis, pneumonia, pyelonephritis, keratitis, and skin infection.3

Cryptococcus laurentii is a urease-positive organism. Gram stain shows large budding yeasts without hyphae. The yeast grows on routine agar as whitish-yellow creamy colonies and on birdseed agar as whitish or greenish colonies. Staining with calcofluor highlights encapsulated yeast forms. Molecular diagnosis can be accomplished by ribosomal RNA sequencing of the internal transcribed spacer and D1/D2 regions. Treatment in most cases has been with fluconazole, although in one case of peritoneal dialysis catheter-related peritonitis, voriconazole was used due to low fluconazole susceptibility.4

References

  1. Molina-Leyva A, Ruiz-Carrascosa JC, Leyva-Garcia A, Husein-Elahmed H. Cutaneous Cryptococcus laurentii infection in an immunocompetent child. International Journal of Infectious Diseases. 2013;17(12). doi:10.1016/j.ijid.2013.04.017.
  2. Johnson, L. B., Bradley, S. F. and Kauffman, C. A. Fungaemia due to Cryptococcus laurentii and a review of non-neoformans cryptococcaemia. Mycoses. 1998;41: 277–280. doi:10.1111/j.1439-0507.1998.tb00338.x
  3. Furman-Kuklińska K, Naumnik B, Myśliwiec M. Fungaemia due to Cryptococcus laurentii as a complication of immunosuppressive therapy – a case report. Advances in Medical Sciences. 2009;54(1). doi:10.2478/v10039-009-0014-7.
  4. Asano M, Mizutani M, Nagahara Y, et al. Successful Treatment of Cryptococcus laurentii Peritonitis in a Patient on Peritoneal Dialysis. Internal Medicine. 2015;54(8):941-944. doi:10.2169/internalmedicine.54.3586.

 

-Prajesh Adhikari, MD is a 3rd year anatomic and clinical pathology resident at the University of Vermont Medical Center.

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-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

Microbiology Case Study: A 62 Year Old Man with a Lung Mass

A 62 year old male without a significant past medical or smoking history was referred to pulmonology for an abnormal chest CT.  Three months prior to presentation, the patient had developed a cough after doing some home remodelling that involved sanding drywall.  The cough became severe and blood-tinged, including some clots, so the patient sought medical attention.  The patient denied any other symptoms and reported feeling well overall.  Physical exam findings were all within normal limits.  A chest X-ray showed a round lesion in the left lower lobe.  Follow-up chest X-rays showed that the lesion had decreased in prominence but had not resolved.  Subsequently, a chest CT was performed that showed a 2.8cm mass-like focal area of consolidation in the left lower lobe without associated lymphadenopathy.  Because malignancy could not be excluded, the patient underwent bronchoscopy with biopsies obtained for cytopathologic evaluation as well as mycobacterial and fungal cultures.

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Image 1: Cytologic preparation (alcohol-fixed, Papanicolaou-stained) of lung, left lower lobe, 2.8cm mass, fine needle aspiration.

The cytologic preparation of fluid from a fine needle aspiration (Image 1) shows granulomatous inflammation with patchy necrosis.  Typically, a mixed inflammatory reaction is observed, with neutrophils, granulomas, epithelioid histiocytes, and foreign body giant cells.  Examination reveals several round-to-oval yeast cells, measuring 9-13μm in diameter.  Single broad-based (4-5 μm wide) buds and thick, double contoured, refractile cell walls are also characteristic of the yeast forms visualized here, leading to a rapid presumptive diagnosis.

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Image 2: Scotch Tape touch preparation of one white colony growing on potato flake agar (25°C) after 10 days of incubation.

Growth of the fungus on various culture media is more sensitive than direct examination and yields a definitive diagnosis.  On potato flake agar incubated at room temperature (25°C), one white colony that was tan on the reverse began growing at 8 days.  Typically, colonies appear in 1-4 weeks and range from white (initially) to brown (with age).  Microscopic examination of a Scotch Tape touch prepared at 10 days (Image 2) demonstrates the mold form of this dimorphic fungus has delicate, septate hyphae with right-angle conidiophores that bear single, terminal conidia (resembling lollipops).  A DNA probe is used to confirm the identification of Blastomyces dermatitidis.

Discussion

As described above, Blastomyces dermatitidis is a thermally dimorphic fungus.  In the environment, the mold form of B. dermatitidis is found in wet soil, particularly when enriched by animal droppings and decaying organic matter (1).  When a susceptible host (healthy or immunocompromised) disrupts wet earth that contains B. dermatitidis, infectious conidia are inhaled into the lungs.  Adult men are more likely to have blastomycosis, likely because they partake in outdoor activities (ex. hunting, fishing) that are associated with environmental exposure to airborne conidia.

Symptoms of blastomycosis are variable, ranging from asymptomatic or transient flu-like to severe pulmonary involvement.  Patients may present with symptoms of acute pneumonia (fevers, chills, cough, hemoptysis, and dyspnea) that can be indistinguishable from viral or bacterial causes.  Other patients, with chronic pneumonia, have systemic symptoms (weight loss, low-grade fevers, night sweats, productive cough, and chest pain) that overlap with pulmonary tuberculosis, histoplasmosis, or bronchogenic malignancy.  In addition to the primary pulmonary infection, approximately half of patients develop extrapulmonary symptoms from hematogenous dissemination to almost any organ; most commonly to skin, bones, male genitourinary, and the central nervous system.

Regardless of symptoms, a majority of patients with blastomycosis will have chest X-ray findings, alveolar infiltrates or a mass lesion involving any location that are non-specific and may mimic malignancy.  The mortality rate is 0% in healthy hosts and up to 30% in immunocompromised people, frequently due to disseminated disease.  There are no guidelines for susceptibility testing of dimorphic fungi.  The preferred treatment of mild to moderate pulmonary blastomycosis is itraconazole for 6-12 months.  Conversely, amphotericin B is used in moderately severe disease to treat chronic pulmonary symptoms, disseminated blastomycosis, CNS involvement, immunocompromised or pregnant patients.

Reference

  1. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23(2):367-81.

 

-Adina Bodolan, MD is a 1st year anatomic and clinical pathology resident at the University of Vermont Medical Center.

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-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

Microbiology Case Study: A 55 Year Old Female with Respiratory Failure

Case History

A 55 year old female with a history of chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, and current tobacco use was transferred to our hospital due to acute hypoxemic respiratory failure. She had a gradual six day onset of cough, fever, malaise, weakness, dizziness and wheezing. At the outside facility, she was hypoxic with an oxygen saturation of 67% at room air, hypotensive with a blood pressure of 80/50. She was intubated en route to our facility.

Labs were significant for a positive influenza B swab, leukopenia (WBC 1.2) with 59% bands, and acute kidney injury with a creatinine of 1.4 mg/dl and hyponatremia with a sodium level of 129 mEq/L. Blood cultures grew Streptococcus pneumoniae, sensitive to ceftriaxone. At our facility, she was started on ceftriaxone and azithromycin. She completed 14 days of ceftriaxone; however, she continued to have intermittent fevers above 38 degrees Celsius. Due to the patient’s continued fever, infectious work up was initiated and showed Candida in her urine and HSV lesions on her lips. She was started on a 14 day course of fluconazole and valacyclovir.

Tracheal aspirates on two occasions were also cultured and grew mixed gram positive and negative organisms as well as Syncephalastrum species. Four weeks after being admitted to our facility, she developed a right-sided hydropneumothorax in which 500 mL of exudative fluid was drawn and subsequently cultured. These cultures also grew Syncephalastrum species as well as Staphylococcus epidermis.

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Image 1: Syncephalastrum growing on a blood agar plate from the patient’s pleural fluid.
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Image 2: Lactophenol cotton blue stain of Syncephalastrum demonstrating the sporangiophore with tubular sporangia on the large round vesicle. The sporangia contain chains of round spores.

Discussion

Syncephalastrum racemosum is thought to be the only species out of the two Syncephalastrum species known to cause mucormycoses in humans (1). The only proven reported cases of infection have been due to percutaneous inoculation after trauma, however whether this is due to low pathogenicity, no case reports, or interpretation as a contaminant remains a mystery (1).

Syncephalastrum is a saprophytic fungus isolated throughout the world particularly in environments with decaying organic matter (1, 2). It is found in low levels in the air and has been reported to colonize both immunocompromised and healthy individuals after natural disasters (3).

Diagnosis of Syncephalastrum can be made by visualizing pauci-septate, ribbon-like mycelium and a merosporangial sack surrounding sporangiospores from the cultures using a lactophenol cotton blue mount preparation (1). Caution should be used in distinguishing Aspergillus niger from Syncephalastrum using a direct KOH mount due to the similarities in their fruiting bodies (1). On a petri plate, it begins as fast growing white fluff and then turns dark gray to almost black with the reverse side being white (4).

 

References

  1. Gomes MZ, Lewis RE, Kontoyiannis DP. Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin Microbiol Rev. 2011;24(2):411-45.
  2. Ribes JA, Vanover-sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000;13(2):236-301.
  3. Rao CY, Kurukularatne C, Garcia-diaz JB, et al. Implications of detecting the mold Syncephalastrum in clinical specimens of New Orleans residents after Hurricanes Katrina and Rita. J Occup Environ Med. 2007;49(4):411-6.
  4. Larone DH. Medically Important Fungi, A Guide to Identification. Amer Society for Microbiology; 2011.

 

-Angela Theiss is a pathology resident at the University of Vermont Medical Center.

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-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

Microbiology Case Study: A 16 Year Old with Rhinosinusitis

Case

A 16-year-old male presented with recurrent sinusitis and rhinitis. He had a history of left sinus surgery two years ago, and at that time pathologic examination of the tissue demonstrated eosinophilia and fungal culture grew Curvularia, consistent allergic fungal sinusitis. The patient was doing well without allergy or immunotherapy management until three months ago when he could not breathe out of the right nostril and began snoring loudly. He underwent bilateral endoscopic frontal sinusotomy with tissue removal of the ethmoid and sphenoid sinuses. Tissue was sent to the laboratory for fungal culture. After five days, fungal cultures grew mold on inhibitory mold agar with gentamicin. The surface was a gray speckled color (Image 1C). The reverse color of the mold colony was dark brown to black. The microscopic appearance can be seen in Image 1A-B.

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Image 1. A) Ellipsoid conidia with the common number of 3-5 septations stained with lactophenol cotton blue counterstain, B) a cluster of conidia surrounded by less lactophenol cotton blue stain better demonstrating brown melanin pigment in the cell wall, and C) a dark gray speckled fungal colony.

 

Discussion

These features are consistent with the identification of Bipolaris. Microscopic examination using lactophenol cotton blue tape prep demonstrated oblong conidia characteristic of Bipolaris (Image 1 A-B). The conidia are ellipsoidal with pale brown pseudoseptations that contain three to five septa. Four septa are the most common. Bipolaris is a dematiaceous fungus, meaning the cell walls contain dark brown melanin pigment. This can be seen by microscopic observation of the fungal cell wall which contains pigment (Image 1B) and is also demonstrated by the dark reverse color of the fungal colony.

To distinguish Bipolaris from Drechslera and Exserohilum, the Germ tube test can be utilized. When conidia are incubated with a drop of water on a glass slide for 8-24 hours, they will begin to form Germ tubes. Bipolaris species germinate from both poles of the oblong conidium at a 180 degree angles (hence the name “Bipolaris”), whereas Exserohilum germinate from just one pole at a 180 degree angle and Dreschslera species germinate at a 90 degree angle from the central cells of the conidium. Dreschslera can be confused for Bipolaris based on colony appearance and microscopic appearance, but unlike Bipolaris, Dreschslera is not associated with human disease.1

Pathogenic strains of Bipolaris include Bipolaris australiensis, Bipolaris hawaiiensis, Bipolaris maydis, Bipolaris melanidis, Bipolaris speicifera, and Bipolaris sorokiniana.2 The most common cause of infection is Bipolaris spifcifera. Bipolaris species are the most common cause of fungal sinusitis in immunocompetent individuals which often presents as allergic rhinitis. Allergic rhinitis could also be a risk factor for acquiring Bipolaris. Treatment often consists of prompt surgical excision to prevent expansion, superficial deformity and dissemination. If fungal chemotherapy is pursued, itraconazole and amphoterin B have been reported as effective agents.3

Bipolaris is one of the most common causes of allergic fungal sinusitis, typified by nasal polyps and mucus plugs consisting of eosinophils, fungal hyphae and Charcot-Leyden crystals. It is a type 1 and 3 hypersensitivity reaction mediated process due to high levels of mold-specific IgE.4 Skin prick testing is also positive in patients with allergic fungal rhinosinusitis (AFRS) which further indicates that the pathophysiology is an immunologic versus infectious process.4 While the exact process of fungal allergic sensitization has not been codified, chitin, a structural fungal protein has been shown to elicit a Th2 immune response.5 It will be interesting to see how this research evolves so that we might one day see why fungi can cause both erosive infections and allergies within human patients.

 

References

  1. Fothergill AW. Identification of Dematiaceous Fungi and Their Role in Human Disease. Clin Infect Dis. 1996; 22 (S2): S179-84.
  2. Shafili SM, Donate G, Mannari RJ, Payne WG, Robson MC. Diagnostic Dilemmas: Cutaneous Fungal Bipolaris Infection. Wounds. 2006; 18(1):19-24.
  3. Saenz RE, Brown WD, Sanders CV. Allergic Bronchopulmonary Disease Caused by Bipolaris hawaiiensisPresenting as a Necrotizing Pneumonia: Case Report and Review of Literature. The American Journal of Medical Sciences. 2001; 321(3):209-12.
  4. Manning SC, Holman M. Further evidence for allergic pathophysiology in allergic fungal sinusitis. Laryngoscope. 1998;108(10):1485–1496.
  5. Reese TA, Liang HETager AMLuster ADVan Rooijen NVoehringer DLocksley RM. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 2007; 3;447(7140):92-6.

 

 JS

-Jeffrey SoRelle, MD, is a 1st year Clinical Pathology Resident at UT Southwestern Medical Center.

Erin McElvania TeKippe, PhD, D(ABMM), is the Director of Clinical Microbiology at Children’s Medical Center in Dallas Texas and an Assistant Professor of Pathology and Pediatrics at University of Texas Southwestern Medical Center.

Microbiology Case Study: A 3 Year Old Girl with Abdominal Pain and Fever

Case History

A 3 year old girl initially presented with abdominal pain and fevers. Ultrasound identified a left kidney mass, leading to a left radical nephrectomy and excision of retroperitoneal mass. Pathology showed a Wilms’ tumor, diffuse anaplasia type. Staging uncovered multiple pulmonary metastases and involvement of a supraclavicular lymph node. She received chemotherapy and radiation without regression of disease.  She then presented to the ED and was admitted for neutropenic fever. She was started on broad-spectrum antibiotics. She continued to spike fevers so an antifungal, micafungin, was added.  While admitted, she developed scattered erythematous papules. Infectious disease was consulted and a skin biopsy from the left forearm was obtained.

Laboratory Results

  • Bacterial cultures, blood: negative
  • Fungal cultures, blood: negative
  • Blastomyces urine antigen: negative
  • Skin biopsy: slight epidermal hyperplasia with follicular dilatation, mild vascular ectasia, and focal erythrocyte extravasation. Negative for organisms.
  • Bacterial culture, tissue: no growth.
  • Gram stain: rare budding yeast forms seen
  • Fungal culture, tissue: no growth to date
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The gram smear made from skin biopsy tissue for bacterial culture displayed rare broad-based budding yeast forms, consistent with Blastomyces dermatiditis.

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The gram smear made from skin biopsy tissue for bacterial culture displayed rare broad-based budding yeast forms, consistent with Blastomyces dermatiditis.

 

Discussion

Blastomyces dermatitidis is a dimorphic fungus found in moist soil and decomposing matter. It is endemic within the Mississippi and Ohio River valleys as well as the Great Lakes region and Southern United States.  There are reports of infection in Africa and India. The fungus is transmitted by inhalation of as few as 10-100 conidia. Once in the lungs, the spores convert to yeast and multiply. Infection usually results in a flu-like illness with pulmonary involvement 3-15 weeks post-exposure. Hematogenous spread can further result in involvement of the skin, bone, genitourinary tract, and central nervous system.

The gold standard for diagnosis is culture or cytopathology/histology. However, the organism is a slow grower, which can take 2-4 weeks, and may fail to grow in one-third of cases. On culture at room temperatures (25-30°C), the mold form appears wrinkled and waxy and is cream to tan in color. Microscopically, they form septate hyphae with short or long conidiophores bearing small round to pear-shaped conidia (2-10 microns). This arrangement of the mold is described as a “lollipop” appearance. At 35-37°C, the fungus is a yeast (8-10 microns) with classic broad-based budding and double contoured walls.

Antigen testing is available on urine, serum, bronchoalveolar lavage fluid, and CSF. Antigen testing is more rapid, utilizing enzyme immunoassay, but has a lower sensitivity. Antigen testing is most sensitive in patients with isolated pulmonary disease. Serial urine antigen testing can be used to indicate disease regression or relapse.

A real-time PCR assay is available for confirmation of B. dermatitidis. The probe targets the promoter region of the BAD1 gene, which encodes an adhesin molecule and virulence factor. This method can be performed in five hours, but is only available at reference laboratories.

Mild to moderate pulmonary and extrapulmonary blastomycosis can be treated with oral itraconazole. Severe cases, CNS involvement, or infection of immunosuppressed patients, pregnant women, or children require amphotericin B followed by step-down therapy with itraconazole for 6-12 months.

Upon report of the mold on gram smear, micafungin was discontinued and amphotericin B treatment initiated. Her fever and rash resolved. The patient was transitioned to oral itraconazole prior to discharge and will remain on therapy for 12 months.

REFERENCES

  1. https://www.cdc.gov/fungal/diseases/blastomycosis/index.html
  2. Frost HM, Novicki TJ. Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis. Journal of Clinical Microbiology. 2015;53(11):3660-3662. doi:10.1128/jcm.02352-15.
  3. Sidamonidze K, Peck MK, Perez M, et al. Real-Time PCR Assay for Identification of Blastomyces dermatitidis in Culture and in Tissue. Journal of Clinical Microbiology. 2012;50(5):1783-1786. doi:10.1128/jcm.00310-12.
  4. Chapman SCAW, Dismukes WE, Proia LA, et al. Clinical Practice Guidelines for the Management of Blastomycosis: 2008 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2008;46(12):1801-1812. doi:10.1086/588300.

 

 

-Prajesh Adhikari, MD is a 2nd year anatomic and clinical pathology resident at the University of Vermont Medical Center.

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-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Assistant Professor at the University of Vermont.