July 2016 Critical Care Case of the Month

Warren Carll, DO

Susanna Tan, MD

Shannon Skinner, MD

Maricopa Integrated Health System

Phoenix, AZ USA

Critical Care Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours 

Lead Author(s): Warren Carll, DO.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

History of Present Illness

The patient is a 20-year-old man with admitted to Maricopa Integrated Health System unconscious after being found down on a hiking trail.

Past Medical History

Hypertension and morbid obesity.

Physical Examination

• Vital signs: BP 90/60 mm Hg, P 128 beats/min, Respiration 28 breaths/min, T 105.8º F, SpO2 98% on 2 L/min by NC.
• General: he is unresponsive to verbal stimuli but withdraws from pain
• Neck: there is no jugular venous distention. Thyroid is not palpable.
• Lungs: clear
• Heart: Regular tachycardia without murmur
• Abdomen: Obese but soft without organomegaly or tendernesses
• Extremities: apparent burns over both lower extremities

Which of the following should be done initially? (Click on the correct answer to proceed to the second of five panels)

1. Cool the patient as quickly as possible
2. Cool the patient slowly to prevent cerebral edema
3. Aggressively administer normal saline to correct hypotension
4. 1 and 3
5. All of the above

Cite as: Carll W, Tan S, Skinner S. July 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;13(1):9-14. doi: http://dx.doi.org/10.13175/swjpcc046-16 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