August 2015 Critical Care Case of the Month: A Diagnostic Branch of Medicine

William T. Love, MD

Karen L. Swanson, DO

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

 History of Present Illness

A 66-year-old man had undergone an orthotopic heart transplantation on March 28th, 2015 due to end-stage cardiomyopathy. During a recent hospitalization from 6/26-7/2 a transbronchial lung biopsy was suggestive of  subacute rejection. He was treated with:

• Plasmapheresis x 3
• Intravenous immunoglobulin (IVIG)
• 500 mg Solu-Medrol daily
• Tacrolimus held as supra-therapeutic level of 16.2
• Mycophenolate decreased to 500mg BID
• Prednisone at 10mg BID on discharge

On July 3rd he began having cough productive of clear sputum, nausea, vomiting, and headache. Subsequently he had body aches, subjective fever, chills, night sweats, and a poor appetite with a 4 kg weight loss over the last week. There was also a history of several falls after “losing his balance".

Past Medical History

There was also a history of type 2 diabetes mellitus, chronic kidney disease, coronary artery disease with coronary artery bypass grafting in 2000.

Physical Examination

• Vital signs: T-37.1, HR-100, BP-130/88, RR-22, 96% RA
• Heart: regular rate & rhythm. 2/6 Systolic Murmur
• Lungs: clear to auscultation bilaterally

Laboratory

• Hemoglobin 9.7, WBC 6.3, creatinine 2.2, mildly elevated AST/ALT
• Lumbar Puncture– Protein 58 mg/dL, Glucose 46 mg/dL, 47 Nucleated cells

Radiography

A chest x-ray was performed (Figure 1).

Figure 1. Admission PA of the chest.

Based on the chest x-ray and lumbar puncture, which of the following are true? (Click on the correct answer to proceed to the second of four panels)

1. The chest x-ray and lumbar puncture findings in this clinical situation suggest cancer metastatic to the lung and brain
2. The chest x-ray and lumbar puncture findings in this clinical setting suggest an infection involving the lung and brain
3. The clinical findings suggest granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)
4. The clinical findings are suggestive of acute rejection
5. The clinical findings are suggestive of tuberculosis

Reference as: Love WT, Swanson KL. August 2015 critical care case of the month: a diagnostic branch of medicine. Southwest J Pulm Crit Care. 2015;11(2):59-65. doi: http://dx.doi.org/10.13175/swjpcc100-15 PDF

January 2015 Critical Care Case of the Month: Who's Your Momma?

Carlos Hartmann, MD

Layth Al-Jashaami, MD

Timothy T. Kuberski, MD

Department of Medicine

Maricopa Integrated Health Services

Phoenix, AZ USA

History of Present Illness

A 39-year-old Hispanic woman was admitted complaining of shortness of breath and bilateral lower extremity edema. She was felt to be in acute hypoxic respiratory failure.

Past Medical History

• Systemic lupus erythematosus
• Congestive heart failure with an ejection fraction of 40%
• End-stage renal disease on dialysis secondary to lupus nephritis

Medications

• Rituximab 550 mg once a week
• Prednisone 40 mg daily
• Plaquenil 200 mg twice a day

Physical Examination

The patient was tachypneic in obvious respiratory distress. She was afebrile. Crackles at the bases. Heart was tachycardic. There was 3+ bilateral pitting pretibial edema.

Laboratory

CBC: Hemoglobin 7.8 g/dL, WBC 11 X 10⁹ cells per liter, differential: neutrophils 98%, eosinophils 0%, lymphocytes 1%.

Electrolytes: Potassium 5.8 mEq/L, sodium 143 mEq/L, creatinine 3.3 g/dL, BUN 98 mg/dL.

Brain naturetic peptide: 4055 pg/ml.

Imaging

Admission chest x-ray showed cardiomegaly and bilateral interstitial prominence suggestive of congestive heart failure.

Which of the following are appropriate initial management? (Click on the correct answer to proceed to the 2nd of 4 panels)

1. Bronchoscopy with bronchoalveolar lavage
2. Hemodialysis
3. Increased methylprednisolone for a potential lupus "flare"
4. 1 and 3
5. All of the above 

Reference as: Hartmann C, Al-Jashaami L, Kuberski TT. January 2015 critical care case of the month: who's your momma? Southwest J Pulm Crit Care. 2015:10(1):11-15. doi: http://dx.doi.org/10.13175/swjpcc145-14 PDF

Life Threatening Zygomyces Infection of the Gastrointestinal Tract

Mohanad Al-Qaisi, MD¹

Charles Stauffer, MD¹

Gerges Makar, MD¹

Tim Kuberski, MD²

¹Department of Medicine, Maricopa Medical Center, Phoenix, Arizona

²Department of Medicine, Infectious Diseases, Maricopa Medical Center, Phoenix, Arizona

Abstract

A 25 year old diabetic woman was admitted into the Intensive Care Unit because of ketoacidosis, hypotension and upper gastrointestinal bleeding. Emergency endoscopic biopsy of the upper gastrointestinal tract demonstrated invasive, non-septate fungal hyphae suggestive of either a Zygomyces or Basidiobolus. Amphotericin B was not used because of its ineffectiveness against Basidiobolus and her renal failure. In addition, first generation antifungal azoles were not used because of their ineffectiveness against Zygomyces. The patient responded to medical therapy and the broad-spectrum azole antifungal posaconazole which has activity against both Basidiobolus and Zygomyces. The patient recovered from her critical illness and on follow up was without residual problems.

Introduction

Zygomyces are a group of fungi which include Mucor, Rhizopus and Absidia, the more common pathologic fungi in the order of Mucorales. As a group, these fungi are characterized by having non-septate hyphae and cause aggressive angioinvasion in certain immunosuppressed settings like ketoacidosis (1). We present a patient who presented with a life-threatening septic syndrome, ketoacidosis and gastrointestinal bleeding due to an infection by an unknown non-septate hyphal fungus, eventually identified as Rhizopus species. On presentation the patient was critically ill and admitted to the Intensive Care Unit. Her early course was complicated by a therapeutic antifungal dilemma which could influence her survival.

Case Report

A 25 years old woman with diabetes was admitted to the Intensive Care Unit with septic syndrome and diabetic ketoacidosis. She was hypotensive, blood pressure was 75/42 mmHg, heart rate 147/min, temperature 38.7 C. Pertinent blood testing revealed the following; glucose 623 mg/dl, creatinine 2.15 mg/dl, bicarbonate 13.6 mmol/L, lactic acid 6.8 mmol/L, WBC 9200/ μL, hemoglobin 7.4 gm/ dl. She was treated aggressively with intubation, mechanical ventilation, vasopressors and continuous renal replacement therapy (CRRT). Her diabetes was treated conventionally. Her course was complicated by a drop in hemoglobin from 11.4 to 7.0 gm/ dl despite transfusions. Her stool was found to be hemoccult positive.

Upper endoscopy showed multiple ulcers involving the gastric body extending onto the cardia which was covered with coffee ground exudate. Biopsies were obtained and showed a "fungus" with non-septate hyphae on preliminary histopathology and amphotericin B was initiated empirically. She continued to experience significant hematemesis and hypotension requiring multiple transfusions (4 units). The amphotericin B was discontinued because of progressive azotemia. Upon review of the pathology from the stomach biopsy, the possibility was raised that she might have either a Basidiobolus or Zygomyces infection (Figure 1).

Figure 1 illustrates the difference in appearance of non-septate hyphae between fungi in tissue in vivo and on culture in vitro. (A) Fungal culture (in vitro) showing the non­ septate hyphae. (B) GMS stain of the stomach tissue from the patient (in vivo) showing fungus fragments having broad, irregular, non-septate hyphae, arrow. The hyphae morphology becomes distorted with angioinvasion and tissue necrosis.

The patient was started empirically on oral posaconazole 400 mg twice daily which theoretically would be effective for both fungi. Within a few days the ketoacidosis resolved, the gastrointestinal bleeding stopped and she was discharged a few days later. After her discharge a Rhizopus species was cultured and identified as the causative agent.

Discussion

The therapeutic dilemma in the treatment of this patient was related to the inability to differentiate between two potential fungal pathogens, Zygomyces or Basidiobolus on the basis of only tissue pathology. Under ideal circumstances the histopathology might differentiate the two, however trying to distinguish between the two can be difficult because both have non-septate hyphae, are morphologically similar, and can involve the stomach. Based on morphology the differentiation between Basidiobolus and Rhizopus is subtle. For Basidiobolus the hyphal elements typically show "sparse" septation while Rhizopus hyphal elements show "infrequent" septation. There was an added problem in that confirmatory cultures can take weeks before a specific identification can be made. Zygomyces infections tend to be rapidly destructive, but are rare to involve the gastrointestinal tract (1). In contrast, Basidiobolus rananum is endemic to Arizona and generally known to primarily cause gastrointestinal infections (2). That organism however, usually causes an indolent process and is less likely to be fatal. However, there is a case report of angioinvasive disease with basidiobolomycosis reminiscent of mucormycosis in diabetics (3). Epidemiological studies on Basidiobolus suggest that the common risks for this infection include living in Arizona, having diabetes and use of medications that suppress stomach acids (2).

A high index of suspicion in our patient with some of these risk factors made Basidiobolus a consideration. Importantly, the antifungal treatment of Basidiobolus is different than for the Zygomyces (i.e., Rhizopus). Basidiobolus is known to be resistant to amphotericin B and the preferred treatment is itraconazole (2).

Our patient initially received a few doses of amphotericin B empirically because of the report of a non-septate "fungus" on biopsy. Amphotericin B is the drug of choice for Zygomyces, but not for Basidiobolus (4). Notably itraconazole is not effective for the Zygomyces. The treatment decision was made to use posaconazole because of its broad spectrum antifungal activity that would have activity against both Zygomyces and Basidiobolus. In addition, there is a report of posaconazole being used successfully to treat gastrointestinal basidiobolomycosis (5). Of the Zygomyces, Rhizopus is the most common cause of human infections, more than Mucor. Certainly correcting the ketoacidosis and gastrointestinal bleeding contributed to her improvement, but the mortality rate in diabetic patients with Zygomyces involving the gastrointestinal tract is about 85% (6). The patient appeared to be effectively treated based on the therapeutic antifungal decision while the patient was critically ill. She was seen in follow up several weeks later without any obvious residual effects. Her response to posaconazole suggests it would be an effective consideration in places like Arizona where Basidiobolus and Zygomyces could be in the differential.

References

1. Chayakulkeeree M, Ghannoum MA, Perfect JR. Zygomycosis: the re-emerging fungal infection. Eur J Clin Microbiol Infect Dis. 2006;25(4):215-29. [CrossRef] [PubMed]
2. Vikram HR, Smilack JD, Leighton JA, Crowell MD, De Petris G.. Emergence of gastrointestinal basidiobolomycosis in the united states, with a review of worldwide cases. Clin Infect Dis. 2012;54(12):1685-91. [CrossRef] [PubMed]
3. Bigliazzi C, Poletti V, Dell'Amore D, Saragoni L, Colby TV. Disseminated basidiobolomycosis in an immunocompetent woman. J Clin Microbiol. 2004;42(3):1367-9. [CrossRef] [PubMed]
4. Guarro J, Aguilar C, Pujol I. In-vitro antifungal susceptibilities of Basidiobolus and Conidiobolus spp. strains. J Antimicrob Chemother. 1999;44(4):557-60. [CrossRef] [PubMed]
5. Rose RR, Lindsby MD, Hurst SF, Paddock CD, Damodaran T, Bennett J. Gastrointestinal basidiobolomycosis treated with posaconazole. Med Mycol Case Rep. 2012;2:11-4. [CrossRef] [PubMed]
6. Roden MM, Zaoutis TE, Buchanon WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, Kontoyiannis DP, Walsh JT. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634-53. [CrossRef] [PubMed]

Reference as: Al-Qaisi M, Stauffer C, Makar G, Kuberski T. Life threatening zygomyces infection of the gastrointestinal tract. Southwest J Pulm Crit Care. 2014;9(2):133-6. doi: http://dx.doi.org/10.13175/swjpcc090-14 PDF 

January Critical Care Case of the Month: Bad Cough

Bhupinder Natt MD

Linda Snyder MD

Janet Campion MD

University of Arizona Medical Center

Tucson, AZ

History of Present Illness

A 41 year-old man was admitted with a five-day history of cough, shortness of breath, and fever to 102° F. He was recently diagnosed with a high-grade astrocytoma of the brain and had undergone resection followed by chemotherapy with temozomide (an alkylating agent) and radiation therapy. 

PMH

• Renal transplantation (1993)
• Glioblastoma (astrocytoma grade 4)
• Crohn’s disease treated with budesonide and meselamine

Medications

• Dexamethasone 2 mg PO BID
• Keppra 500 mg PO BID
• Tacrolimus 1.5 mg PO AM and 1mg PO PM
• Mycophenolate 750 mg PO BID
• Budesonide 3 mg PO daily
• Meselamine 1600 mg PO TID
• Sulfamethoxazole/trimethoprim DS PO on Mon/Wed/Fri
• Temozolomide 75 mg IM with radiotherapy

Social History

Nonsmoker, no ethanol or recreational drugs, no recent travel, and no occupational exposures.

Physical Examination

T 38.6°C, P 112 beats/min, RR 32-40 breaths/min, BP 119/76 mm Hg, SpO2 100% on NRB

General: Fatigued, ill appearing and dyspneic.

Skin: No rash or lesions, well-healed craniotomy scar

HEENT: Dry oral mucosa, pupils and extra-ocular muscles normal

Respiratory: Reduced breath sounds, fine crackles throughout all lung fields, no wheezing

CVS: Hyperdynamic precordium, tachycardia without murmur, no elevation of jugular venous pressure (JVP), peripheral vascular exam normal.

Abdomen: Soft, non-distended, no hepato-splenomegaly, normal bowel sounds.

Lymph: No cervical lymphadenopathy

Extremities: No edema, normal muscle bulk and tone.

Laboratory

WBC 11 X 10³/µL, Hemoglobin 9.8 g/dL, Hematocrit 30%, Platelets 264,000/ µL

Na⁺ 135 meq/L, K⁺ 4.2 meq/L, Cl⁻ 111 meq/L, CO2 14 mmol/L, blood urea nitrogen (BUN) 46 mg/dL, creatinine 1.7 mg/dL, glucose 132 mg/dL, calcium 10.5 mg/dL, albumin 1.5 g/dL, liver function tests-within normal limits

Prothrombin time (PT) 15 sec, international normalized ratio (INR) 1.2, partial thromboplastin time (PTT) 29.9 sec

Chest X-ray

Figure 1. Admission PA (Panel A) and lateral (Panel B) chest x-ray.

What is the best description of the chest x-ray? (click on correct answer to move to next panel)

1. Bibasilar consolidation
2. Bilateral diffuse nodules
3. Pneumomediastinum with subcutaneous emphysema
4. Pulmonary edema with evidence of pulmonary hypertension
5. Subdiaphragmatic free air

Reference as: Natt B, Snyder L, Campion J. January critical care case of the month: bad cough. Southwest J Pulm Crit Care. 2014;8(1):20-6. doi: http://dx.doi.org/10.13175/swjpcc161-13 PDF

November 2013 Critical Care Case of the Month: A Series of Unfortunate Infections

Kenneth K. Sakata, MD

Karen L. Sapienza, MD

Lewis J. Wesselius, MD 

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 22 year old man was admitted with fever for 2 weeks. He had a history of acute lymphocytic leukemia (ALL) and had received a stem cell transplant in (SCT) in May 2013.

PMH, SH, FH

Other than the ALL and STC transplant there was no significant PMH, SH, or FH. The STC was uneventful.

Physical Examination

T 38.6°C with a pulse of 110 beats/min. Otherwise the physical examination was unremarkable.

CT scan

A CT scan of the thorax was performed in a search for the source of the fever (Figure 1).

Figure 1. Admission thoracic CT scan showing an abnormality. The remainder of the CT scan was unremarkable.

Which of the following best describes the CT abnormality?

1. Chest wall abnormality in the left chest
2. Focal area of consolidation in the left lung
3. Focal area of consolidation in the right lung
4. Mass in the left lung
5. Mass in the right lung

Reference as: Sakata KK, Sapienza KL, Wesselius LJ. November 2013 pulmonary case of the month: a series of unfortunate infections. Southwest J Pulm Crit Care. 2013;7(5):280-8. doi: http://dx.doi.org/10.13175/swjpcc139-13 PDF