Clinical Performance Of An Automated Systemic Inflammatory Response Syndrome (SIRS) / Organ Dysfunction Alert: A System-Based Patient Safety Project

Robert A Raschke, MD, MS

Huw Owen-Reece, MBBS

Hargobind Khurana, MD 

Robert H Groves Jr, MD

Steven C Curry, MD

Mary Martin, PharmD

Brenda Stoffer

Suresh Uppalapu, MD 

Heemesh Seth, DO

Nithya Menon, MD 

Banner Good Samaritan Medical Center, Phoenix Arizona

Abstract

Objective: We have employed our electronic medical record (EMR) in an effort to identify patients at the onset of severe sepsis through an automated analysis that identifies simultaneous occurrence of systemic inflammatory response syndrome (SIRS) and organ dysfunction. The purpose of this study was to determine the positive predictive value of this alert for severe sepsis and other important outcomes in hospitalized adults.

Design: Prospective cohort.

Setting: Banner Good Samaritan Medical Center, Phoenix AZ

Patients: Forty adult inpatients who triggered alert logic within our EMR indicating simultaneous occurrence of SIRS and organ dysfunction.

Interventions: Interview of bedside nurse and chart review within six hours of alert firing to determine the clinical event that triggered each alert.

Results: Eleven of 40 patients (28%) had a major clinical event (immediately life-threatening illness) associated with the alert firing. Severe sepsis or septic shock accounted for four of these – yielding a positive predictive value of 0.10 (95%CI: 0.04-0.23) of the alert for detection of severe sepsis. The positive predictive value of the alert for detection of major clinical events was 0.28 (95%CI: 0.16-0.43), and for detecting either a major or minor clinical event was 0.45 (95%CI: 0.31-0.60). Twenty-two of 40 patients (55%) experienced a false alert.

Conclusions: Our first-generation SIRS/organ dysfunction alert has a low positive predictive value for severe sepsis, and generates many false alerts, but shows promise for the detection of acute clinical events that require immediate attention. We are currently investigating refinements of our automated alert system which we believe have potential to enhance patient safety.

Introduction

Severe sepsis is defined as systemic inflammatory response syndrome (SIRS) of infectious etiology with secondary organ dysfunction. It is estimated that 750,000 patients suffer severe sepsis annually in the United States - 3 cases per 1000 population (1). Mortality has fallen over the past several decades, but ranges from 20-30% in recent studies (1,3). Results of recent treatment trials for severe sepsis are consistent with the hypothesis that early diagnosis and treatment are important (2,3), but reliable systems for early recognition of severe sepsis in hospitalized patients are not widely available.  

We have sought to improve patient safety at our institution by using our integrated electronic medical record (EMR) to identify patients at the onset of severe sepsis through a logic algorithm that analyzes vital signs and laboratory data. This logic function identifies patients with simultaneous systemic inflammatory response syndrome (SIRS) and organ dysfunction, but cannot distinguish whether an acute infection is the cause of these findings. The purpose of this study was to determine what clinical events – infectious or non-infectious - actually cause the vital sign and laboratory changes that trigger this alert, and what the positive predictive valve of the alert is for detecting the onset of severe sepsis in hospitalized adult patients.

Methods

This was a prospective cohort study carried out at Banner Good Samaritan Medical Center – a 700-bed University-affiliated teaching hospital in Phoenix AZ. It was part of an ongoing quality improvement project and was thereby exempted from IRB approval. The SIRS / organ dysfunction alert logic was developed at Banner Health using Cerner Discern Expert^®, Cerner Corporation, North Kansas City MO, USA. The logic function monitored the EMR for standard SIRS criteria and laboratory evidence of organ dysfunction with thresholds consistent with standard definition of severe sepsis (Table 1) (4,5).

Table 1. Specific criteria for the logic function of our SIRS/organ failure alert. 

When any single criterion for SIRS was met, the program searched the prior 6 hours for the most recent vital signs, and the prior 30 hours for the most recent white blood cell count. If a second SIRS criterion was met, the program identified the patient as exhibiting SIRS, but did not trigger an alert. When any single laboratory criterion for organ dysfunction was met (table 1), the program identified the patient as suffering organ dysfunction. If criteria for SIRS and organ dysfunction overlap in any 8 hour window, the alert fired, triggering a real-time notification in the Cerner Millenium^® EMR alerting clinicians to the possibility of severe sepsis or septic shock. The alert has been in clinical application since 2010. 

We sampled 40 non-consecutive inpatients in the first three months of 2014 by a nonrandom method blinded to the patient’s clinical condition. On days of data collection, all alerts that had fired within the prior 6 hours were reviewed, regardless of patient location or diagnosis. The patient bedside was visited by a physician researcher during the six-hour window after alert firing and the nurse interviewed in order to determine the circumstances that caused the alert to fire. The patient might be briefly examined if necessary to confirm the nursing impression. Chart review was also performed to assist in this determination. Demographics, admission diagnosis, vital signs and laboratory data that triggered the alert logic, and any treatment the associated clinical event required were also recorded. Chart review was repeated 48 hours later to review microbiological test results and physician progress notes that might shed further light on the clinical event that triggered the alert.

The “clinical event” associated with each alert was defined as the most likely acute explanation for the vital sign and laboratory abnormalities that triggered the alert. A clinical event might be an acute illness, such as pneumonia with septic shock, or a non-illness event, such as initiation of dialysis. Clinical events could include the illness that necessitated admission if the alert fired within 24 hours of admission, or secondary illnesses - for instance, a catheter-associated blood stream infection.

The severity of clinical events related to alert firings were classified into three tiers. 

1. Major clinical events were acute life-threatening illnesses that required emergent resuscitation with any one or more of the following: >1 L intravenous fluid resuscitation, vasopressor infusion, >2 units of packed red blood cell transfusion, endotracheal intubation, advanced cardiac life support, or emergent surgical intervention.
2. Minor clinical events were acute non-life-threatening illnesses that required urgent treatments not included in the definition of major clinical events above.
3. False alerts were said to have occurred when no acute illness was recognized in temporal relationship to the alert firing. 

The positive predictive value of the alert for detecting severe sepsis, major clinical events, and major or minor clinical events were calculated, with 95% confidence intervals.

Results

Nineteen women and 21 men, with ages ranging from 22 to 103 years were included. Twenty-two of forty (55%) were in the ICU at the time the alert fired, and 18 on the floors. Vital signs and laboratory values that triggered the alert logic are listed in Table 2. 

Table 2. SIRS / organ dysfunction alert trigger criteria in forty patients. 

Eleven of 40 patients (28%) had a major clinical event associated with the alert firing – two of these occurred outside the ICU. Severe sepsis or septic shock accounted for four of these major clinical events – yielding a positive predictive value of 0.10 (95%CI: 0.04-0.23) of the alert for detection of severe sepsis or septic shock. The seven remaining patients with major events suffered acute pulmonary edema, pulmonary embolism, ischemic bowel, pancreatitis, acute cardiogenic shock, acute right heart failure secondary to pulmonary hypertension, and an incarcerated enteric hernia. The positive predictive value of the alert for detection of major clinical events was 0.28 (95%CI: 0.16-0.43).

Major clinical events were clearly recognized before the alert fired in nine of 11 cases, as evidenced by the patient having been admitted or transferred to the intensive care unit specifically for the event of interest, and/or having received treatment such as intubation or initiation of intravenous vasopressors before the alert fired. In two cases, the alert fired at about the same time that treatment of the acute clinical event commenced, and it was unclear what role it played in clinical recognition of the event.

Seven of 40 patients (17%) had a minor clinical event associated with the alert firing. These included two patients with anemia, and one each with hypotension from an antihypertensive medication, dialysis disequilibrium, post-operative pain, dehydration, and paroxysmal atrial fibrillation. The positive predictive value of the alert for detecting either a major or minor clinical event was 0.45 (95%CI: 0.31-0.60).

Twenty-two of 40 patients (55%) were not experiencing any identifiable acute illness that could explain the alert firing - these were considered false alerts. Aberrant vital signs triggered false alerts during dialysis (2), turning or sitting-up post-operative patients (2), an endoscopy procedure, and a family argument. Other false alerts were attributable to the pharmacological effect of calcium channel blocker, oximeter malfunction, error in vital sign entry, and widely discrepant blood pressures between right and left arms. The remaining false alerts were triggered by slightly abnormal vital signs with no identifiable cause.

Four patients (10%) did not survive to discharge – two had major clinical events, one a minor clinical event and one a false alert – in the later two cases, the cause of death was unrelated to the clinical event that triggered the alert.  

We examined alert triggering criteria to better understand how the discriminant ability of the alert might be improved. We noted that 15 of 40 (37%) alerts triggered with respiratory rates of 21 or 22 bpm, however these included six alerts associated with major clinical events. Twelve of 40 (30%) alerts triggered with heart rates in 91-95 bpm range, including two alerts associated with major clinical events. Laboratory results contributed to 31 of 40 alert firings – but in 12 cases they were stable or improving at the time they triggered the alert. In no case was a stable or improving laboratory value associated with a major clinical event.

Discussion

It’s important to study the effects of any quality improvement project in order to determine whether it is having the desired results. Our small pilot study suggests that our first-generation SIRS/organ dysfunction alert has a low positive predictive value for severe sepsis, and generates many false alerts. This is partially a reflection of the low specificity of SIRS criteria for sepsis (6). The high number of false positive alerts has led to alert-fatigue among physicians and nurses providing bedside patient care – a phenomenon which is not unique to our institution (7).  

Our alert demonstrated greater potential utility to detect acute clinical deterioration than to detect sepsis. Buck and colleagues (7) used an EMR-based logic system to activate a sepsis alert similar to ours, and observed similar results in that only 17% of alert patients had a sepsis-related discharge diagnosis, but 40% had a major illness which required urgent intervention. We have used the results of our study to re-task future iterations of our alert to detect acute clinical deterioration rather than sepsis.

Other researchers provide guidance in this regard. Vital sign and laboratory result criteria similar to the ones used in our study have been previously shown to predict in-hospital cardiac arrest (8), predict 30-day mortality (9), generate early warning scores to detect acute clinical deterioration (9), and activate medical emergency teams (8,10). A recent large study by Churpek and colleagues (11) validated a risk stratification tool that utilized vital signs, laboratory findings and demographics to predict the combined outcome of cardiac arrest, ICU transfer or death on the wards. The model yielded notable discriminant accuracy with an area under the receiver operating curve (AUROC) of 0.77.

We are currently investigating revisions in our alert logic to improve detection of acute clinical deterioration. The alert logic now trends laboratory values associated with organ dysfunction. We are studying whether adding a reflex serum lactate to the automatic alert response might help identify patients who are acutely deteriorating (12).   

Our study has many apparent weaknesses, but it should be noted that it was carried out originally only to provide data to help guide local efforts to improve patient safety. In this regard, it succeeded in guiding our (and perhaps other’s) future efforts in what will more likely be a useful direction.

We failed to clearly determine what role our automated alert played in bedside decision-making. In most cases, clinicians were already evaluating or treating the clinical event that triggered the alert before the alert fired. However, we feel that a safety net is a wise precaution even in a high-reliability system. It should also be noted that our institution has medicine and surgery residency teaching programs, a critical care fellowship, 24/7 in-house intensivist coverage, and remote video ICU coverage. The benefit of EMR-based automated alerts is likely to be amplified in less well-staffed institutions. Refined versions of EMR-based automated alerts, such as the ones we are currently investigating, have potential to enhance patient safety. 

References

1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-10. [CrossRef] [PubMed]
2. Rivers E, Nguyen B, Havstad S, Ressler J, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77. [CrossRef] [PubMed]
3. The ProCESS investigators. A randomized controlled trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-93. [CrossRef] [PubMed]
4. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250-6. [CrossRef] [PubMed]
5. Dellinger RP, Levy MM, Rhodes A, et al, Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580. [CrossRef] [PubMed]
6. Pittet D, Range-Frausto S, Tarara LN, et al. Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients. Intensive Care Med. 1995;21:302-9. [CrossRef] [PubMed]
7. Buck KM. Developing an early sepsis alert program. J Nurs Care Qual. 2014;29(2):124-32. [CrossRef] [PubMed]
8. Hodgetts TJ, Kenward G, Ioannis G, et al. The identification of risk factors for cardiac arrest and formulation of activation criteria to alert a medical emergency team. Resuscitation. 2002;54:125-31. [CrossRef] [PubMed]
9. Goldhill DR, McNarry AF. Physiological abnormalities in early warning scores are related to mortality in adult inpatients. Br J Anaesth. 2004;92:882-4. [CrossRef] [PubMed]
10. Kenward G, Castle N, Hodgetts T, Shaikh L. Evaluation of a medical emergency team one year after implementation. Resuscitation. 2004;61:257-63. [CrossRef] [PubMed]
11. Churpek MM, Yuen TC, Winslow C, et al. Multicenter development of validation of a risk stratification tool for ward patients. Am J Respir Crit Care Med. 2014;190:649-55. [CrossRef] [PubMed]
12. Bakker J, Nijsten MWN, Jansen TC. Clinical use of the lactate monitoring in critically-ill patients. Ann Intensive Care. 2013;3:12-20. [CrossRef] [PubMed] 

Reference as: Raschke RA, Owen-Reece H, Khurana H, Groves RH Jr, Curry SC, Martin M, Stoffer B, Uppalapu S, Seth H, Menon N. Clinical performance of an automated systemic inflammatory response syndrome (sirs) / organ dysfunction alert: a system-based patient safety project. Southwest J Pulm Crit Care. 2014;9(4):223-9. doi: http://dx.doi.org/10.13175/swjpcc121-14 PDF

October 2014 Critical Care Case of the Month: A Skin Rash in the ICU

Robert A. Raschke, MD

Banner Good Samaritan Medical Center

Phoenix, AZ

History of Present Illness

A 28 year old man was admitted to an outside hospital with an ethylene glycol overdose in an apparent suicide attempt. At that time the patient was delirious and vomiting. He had a severe metabolic acidosis and a creatinine of 2.1 mg/dL. He was intubated, a nasogastric tube was placed, and he was transferred to the toxicology service.

PMH, FH, SH

There was no significant past medical history. Family history was noncontributory. He was a nonsmoker who recently had a fight with his girlfriend prompting the suicide attempt.

Physical Examination

Vital signs were stable and he was sedated and nasally intubated receiving mechanical ventilation. There were no other significant findings on physical examination

Which of the following can be used for ethylene glycol poisoning? (Click on the correct answer to proceed to the next of 5 panels)

1. Ethanol
2. Fomezipole
3. Hemodialysis
4. Pyridoxine
5. All of the above

Reference as: Raschke RA. October 2014 critical care case of the month: a skin rash in the ICU. Southwest J Crit Care Med. 2014;9(4):208-13. doi: http://dx.doi.org/10.13175/swjpcc110-14 PDF

Ultrasound for Critical Care Physicians: A Tempting Dilemma

Issam Marzouk MD

Lana Melendres MD

Michel Boivin MD

Division of Pulmonary, Critical Care and Sleep

Department of Medicine

University of New Mexico School of Medicine

MSC 10-5550

Albuquerque, NM 87131 USA

A 46 year old woman presented with progressive severe hypoxemia and a chronic appearing pulmonary embolus on chest CT angiogram to the intensive care unit. The patient was hemodynamically stable, but had an oxygen saturation of 86% on a high-flow 100% oxygen mask. The patient had been previously investigated for interstitial lung disease over the past 2 year, this was felt to be due to non-specific interstitial pneumonitis. Her echocardiogram findings are as presented below (Figures 1 and 2).

Figure 1. Parasternal long axis view. Upper panel: static image. Lower panel: video.

 

Figure 2. Apical four chamber view. Upper panel: static image. Lower panel: video

The patient had refractory hypoxemia despite trials of high flow oxygen and non-invasive positive pressure ventilation. She had mild symptoms at rest but experienced severe activity intolerance secondary to exertional dyspnea. Vitals including blood pressure remained stable and normal during admission and the patient had a pulsus paradoxus measurement of < 10 mmHg. She had previously had an echocardiogram 6 months before that revealed significant pulmonary hypertension.

What would be the most appropriate next step regarding management of her echocardiogram findings? (click on the correct answer to move to the next panel)

1. Diagnostic pericardiocentesis
2. Urgent therapeutic pericardiocentesis
3. Avoid pericardiocentesis at this time
4. Urgent thrombolysis with tissue plasminogen activator

Reference as: Marzouk I, Melendres L, Boivin M. Ultrasound for critical care physicians: a tempting dilemma. Southwest J Pulm Crit Care. 2014;9(3):193-6. doi: http://dx.doi.org/10.13175/swjpcc128-14 PDF

September 2014 Critical Care Case of the Month: Bad Case of Colic

Sherry Andrews MD

Eyad Almasri MD

Pulmonary and Critical Care

UCSF Fresno

Fresno, CA

History of Present Illness:

A 70 year old man with a past medical history of chronic kidney disease, bipolar disorder, benign prostatic hypertrophy, hypertension and diabetes presented to the emergency department with constipation associated with bloating for 15 days. He denies flatus. He tried over the counter laxatives (polyethylene glycol) with no relief. He has no recent history of colonoscopy or recent antibiotic use. He denies chills, diarrhea, dysuria, fever, hematochezia, hematuria, melena, nausea or vomiting. In the emergency department, he is tachypneic with a grossly distended abdomen.

Past Medical History:

• Diabetes
• Hypertension
• Chronic kidney disease
• Bipolar disorder
• Benign prostatic hypertrophy
• Hyperlipidemia

Past Surgical History:

• Cholecystectomy 2012

Medications:

• Aspirin 81 mg daily
• Furosemide 20 mg daily
• Quetiapine 300 daily
• Doxazosin- 4 mg daily
• Clonazepam 1 mg – twice daily as needed
• Simvastatin 20 mg – daily
• Pioglitazone 15 mg daily

Social History:

He is a retired farm laborer and worked in a cannery. He is married and has two adult children.

He was a former smoker and quit in 2010 He denies any alcohol or illicit drug use

Physical Exam:

• Vital signs – Temperature 37.2 °C, heart rate 84 beats/min, respiratory rate 18-24 breaths/min, blood pressure 121/83 mmHg, SpO2 94 % on 4 L NC 
• General – Average build, well-nourished, in mild distress
• HEENT – Unremarkable
• Neck - Supple, no jugular venous distention
• Chest – Decreased breath sounds right base more than left base
• Heart - Regular rate, normal S1/S2, no murmur
• Abdomen – hypoactive bowel sounds, soft, distended, non-tender to palpation but diffusely tympanic.
• Neurological - Appropriately moves all 4 extremities, CN II-XII grossly intact
• Extremities - No edema
• Skin - No rash or palpable nodules

Laboratory:

• CBC: WBC 6.4 X 10³ /μL, hemoglobin 15.3 g/dL, hematocrit 45%, Platelets 121,000 /μL.
• Chemistries: Na⁺ 141 mmol/L, K⁺ 4.5 mmol /L, Cl^- 105 mmol /L, CO₂ 25 mmol /L, blood urea nitrogen (BUN) 24 mg/dL, creatinine 1.2 mg/dL, glucose 95 mg/dL, calcium 9.9 mg/dL, albumin 4.2 g/dL, liver function tests within normal limits. hemoglobin A1C 5.1%. lactic acid 1.8 mmol/L
•  Coagulation: Prothrombin time (PT) 16.6 sec, international normalized ratio (INR) 1.3

Radiography:

A CT scan abdomen and pelvis was done and a representative coronal view is shown in Figure 1.

Panel 1. Coronal cut of computed Tomography (CT) of the abdomen and pelvis on admission.

Which of the following are characteristics of acute colonic pseudo-obstruction (Ogilvie’s syndrome)? (Click on the correct answer to proceed to the next panel)

1. Antibiotics and abnormal bacterial overgrowth are implicated in the pathogenesis
2. Immediate surgical decompression is required
3. It is a complication of inflammatory bowel disease
4. It occurs in the absence of an anatomic lesion that obstructs the flow of intestinal contents

Reference as: Andrews S, Almasri E. September 2014 critical care case of the month: bad case of colic. Southwest J Pulm Crit Care. 2014;9(3):151-9. doi: http://dx.doi.org/10.13175/swjpcc094-14 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