Microbiology Case Study

Patient History:

81 year old man with a history of systemic vasculitis (present for the past 10 years ANCA negative, ANA negative, Rheumatoid factor <20) on immunosuppression (plaquenil with prednisone 40mg for flares about every 6 months), type 2 diabetes, and hypertension presented to an outside hospital with weakness and dyspnea. He was found to have a widespread purpura, ulcerative lesions, acute kidney injury (creatinine 4.7), and 3 days of hematochezia. He was started on 7 days of levoquin and zosyn for a presumed pneumonia and with no improvement was transferred to our institution. On admission, a CT scan of the chest demonstrated bilateral multifocal pneumonia and multiple cavitary nodules within the lungs. A thoracentesis was performed and was transudative (wbc 1883, N 63%, protein 2.6).

Laboratory findings:

  • WBC 7000/cmm
  • Hemoglobin 9 g/dL
  • Platelet count 104 K/cmm
  • Bacterial culture blood, no growth
  • Cryptococcal antigen negative
  • Pleural fluid bacterial culture and smear negative
  • Pleural fluid AFB culture and smear – no acid fast bacilli, modified acid fast bacilli seen from bottle
  • Pleural fluid fungal culture and smear – no fungi seen, rare modified acid fast bacilli growing
  • Histoplasma urinary antigen positive
  • Histoplasma antibodies negative
  • Blastomyces urinary antigen negative
Gram stain of growth from the AFB bottle showing beaded, branch Gram positive bacilli.
Gram stain of growth from the AFB bottle showing beaded, branch Gram positive bacilli.
Modified acid fast stain of growth from the AFB bottle showing modified acid fast bacilli.
Modified acid fast stain of growth from the AFB bottle showing modified acid fast bacilli.
Isolated growth on BCYE media.
Isolated growth on BCYE media.

Discussion:

Based on Gram stain and modified acid fast stain, modified acid fast bacilli suggestive of Nocardia species was reported. Nocardia are strict aerobic, gram positive, filamentous rods that stain partially acid fast. This is due to the mycolic acids in the cell wall which are shorter than those of mycobacteria. Nocardia species produce many virulence factors including Cord factor (prevents intracellular killing), catalase and superoxide dismutase (which inactivate reactive oxygen species that would otherwise prove toxic to the bacteria).

Nocardia grow well on buffered charcoal yeast extract agar and at 30oC. They produce aerial hyphae and can have a chalky colony appearance. Species level identification is best done with molecular methods. This isolate was identified as Nocardia farcinica at a reference laboratory.

Nocardia species are ubiquitous in the soil. They can cause infections in immunocompromised hosts usually after inhalation or direct inoculation. Infections include bronchopulmonary disease and cutaneous infections. With bronchopulmonary disease, cavitation and spread to the pleura is common, which fits with our patient. Dissemination is also seen with common sites being brain and subcutaneous tissue.

Our patient had a positive Histoplasma urinary antigen, but negative Histoplasma antibodies. The working diagnosis was disseminated Histoplasmosis and he was being treated with amphotericin B. He expired and no postmortem exam was performed. Fungal cultures from the pleural fluid were not growing fungus at the time of this post. Fungal cultures were not obtained from sputum and a BAL was not performed.

-Dan Olsen, MD is a 4th 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.

There’s a Fungus Among Us

A 53 year old man with history of stroke, alcoholism, heart failure, hypertension, and atrophic right kidney presented to the ED with acute urinary retention and complained of dysuria and frequency. He was afebrile, denied nausea/vomiting or headaches. His labs at admission are listed below:

  • WBC: 21 k
  • Na: 122
  • Cr: 3 (baseline 1.2)

Urinalysis showed innumerable white blood cells, leukocyte esterase 3+ and negative nitrite.

A catheter was placed and drained 1 L of yellow cloudy urine. The patient refused admission and he was prescribed ciprofloxacin 500 mg BID empirically and was sent home with a foley catheter in place with plans to follow up with Urology. He returned to the ED the following day because his foley catheter was not draining urine and he noted leaking around his catheter. CT scan was obtained and showed ill-defined areas of increased and decreased attenuation within the urinary bladder lumen and left hydroureteronephrosis.

fungusball1

Urine cultures obtained during his initial presentation grew >100,000 yeast and he was treated with fluconazole. The patient was taken to the operating room 11 days after first presentation to diagnose and treat the mass in the bladder. A tan-brown mass was removed and send to surgical pathology. Representative section (H&E stain) of the specimen is shown below:

fungusball2

Which of the following statements regarding Candiduria is true?

  1. Most patients with candiduria are asymptomatic and the yeasts merely represent colonization
  2. The presence of pseudohyphae in the urine or the number of colonies growing in culture help to distinguish colonization from infection
  3. The most commonly involved organ in disseminated candidiasis is the heart
  4. There is a higher propensity for fungal ball formation in adults than children

The correct answer is 1. Most patients with candiduria are asymptomatic and the yeast merely represent colonization. Infected patients may have symptoms (dysuria, frequency, suprapubic discomfort) while others might not. Pyuria is so common in patients with a chronic indwelling bladder catheter that it cannot be used to indicate infection.

Neither the presence of pseudohyphae in the urine nor the number of colonies growing in culture (unlike bacterial cultures) help to distinguish colonization from infection. Ascending infections are rare but usually subacute or chronic, unilateral and can cause perinephric abscesses.

Fungus balls in adults are uncommon with less than 10 adult cases reported in the literature. Risk factors include uncontrolled diabetes, prolonged use of antibiotics or steroids and immune compromise. Classic laboratory findings include marked leukocytosis, pyuria, hematuria and a concomitant bacterial urinary tract infection. Most cases are caused by Candida species although Aspergillus has been implicated in a few cases.

The kidneys are the most commonly involved organ in disseminated candidiasis and there is a higher propensity of fungus ball formation in neonates.

-Agnes Balla, 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 Assistant Professor at the University of Vermont.

Why Do Two When One Will Do?

Today I attended a great session on transfusion case studies by Carolyn D. Burns, MD, FASCP, and Phillip J. DeChristopher, MD, PhD, FASCP. The speakers were dynamic, personable, and made learning fun. They presented cases on hematology/oncology, transplant recipients, and HLA antibodies, among others. I won’t go over each case—honestly, there was so much great information I’m afraid I won’t do it justice—but I’d like to share tidbits I found interesting.

-A fact that I had forgotten from my blood banking class oh-so-long-ago: the platelets your body makes live for eight to ten days, an autologous platelet transfusion last four days, and a non-autologous transfusion would last three. If a patient has an immune response to a platelet reaction, those platelet might only live a day.

-Fellows and residents in transfusion medicine don’t actually know how to transfuse a unit of blood product. They aren’t aware of what happens in a blood bank or a transfusion center. Laboratory professionals need to be cognizant of this and be open with information. Use teaching moments when they present themselves.

-Eliminate unnecessary transfusions through dialogue with doctor and pathology. Hence the title of this post: “why do two when one will do?” It’s a mantra for the blood banker to live by.

-Don’t be afraid to question orders. Medical technologists might be the first line of defense, so to speak, and are essential when bringing questionable orders to the attention of pathologists. Don’t be afraid to speak up when your instincts are telling you something is off. Hone your critical thinking skills.

-Blood transfusion is like marriage. It should not be entered upon lightly, wantonly or more often than is absolutely necessary.

-This couldn’t be stressed enough: keep the lines of communication open. Ask the doctor and/or nurse questions about the patient; have a open relationship with your medical director; don’t be afraid to ask questions.