Mycology
A cluster of mucormycosis infections in hematology patients: challenges in investigation and control of invasive mold infections in high-risk patient populations,☆☆,,★★

https://doi.org/10.1016/j.diagmicrobio.2010.12.022Get rights and content

Abstract

Mucormycosis has been reported to be occurring more frequently in hematopoietic stem cell transplant (HSCT) recipients in recent years. We investigated a hospital cluster of mucormycosis cases among patients with hematologic disorders. Case-patients were identified through hospital microbiology and pathology database searches and compared to randomly selected controls matched on underlying disease and hospital discharge date using conditional logistic regression. Environmental assessments, including collection of samples for fungal cultures, were performed. Of 11 case-patients, 6 (55%) had acute myelogenous leukemia and 3 (27%) were allogeneic HSCT recipients. Five case-patients (45%) died. In univariate analysis, case-patients were more likely than controls to have refractory hematologic disease (odds ratio [OR], 13.75; 95% confidence interval [CI], 1.31–689); neutropenia >14 days (OR, 11.50; 95% CI, 1.27–558) or to have received voriconazole prophylaxis (OR, 11.26; 95% CI, 1.11–infinity). A point source was not identified. Factors such as underlying disease state and antifungal prophylaxis type may identify hematology patients at highest risk for mucormycosis. Our investigation highlighted critical knowledge gaps, including strain typing methods, the role of the hospital environment in mucormycosis outbreaks, and hospital environmental infection control measures most likely to reduce exposure of immunosuppressed persons to mucormycetes.

Introduction

Mucormycosis, also known as zygomycosis, is increasingly recognized as an important cause of morbidity and mortality among immunosuppressed persons. Although there are no recent population-based estimates of mucormycosis incidence, some investigators have reported increases in the incidence or number of cases occurring in hematopoietic stem cell transplant (HSCT) recipients and patients with hematologic malignancies over the past 2 decades (Imhof et al., 2004, Kontoyiannis et al., 2000, Kontoyiannis et al., 2005, Marr et al., 2002, Marty et al., 2004, Roden et al., 2005, Siwek et al., 2004, Vigouroux et al., 2005). Advances in cancer treatment and supportive care have likely increased the lifespan of patients with active but stable cancer; persons with hematologic malignancies treated in recent years may therefore be at risk for longer periods of time for the development of a variety of opportunistic infections, including mucormycosis, due to treatment- and disease-related immunosuppression.

Mucormycosis may be acquired in community or health care settings. Published guidelines (Centers for Disease Control and Prevention, 2000, Centers for Disease Control and Prevention, 2003, Yokoe et al., 2009) and facility design standards for units housing HSCT recipients (American Institute of Architects and Facilities Guidelines Institute, 2006) provide recommendations for reducing health care setting-related mold exposure of high-risk patients. These guidelines recommend that allogeneic HSCT recipients be housed in Protective Environment inpatient rooms, with high-efficiency particulate air (HEPA) filtration, room air exchange rates of ≥12 air changes per hour (ACH), and positive pressure of ≥2.5 Pa with respect to the corridor (Centers for Disease Control and Prevention, 2000, Centers for Disease Control and Prevention, 2003, Yokoe et al., 2009). These recommendations are applicable to facilities that are newly constructed or undergoing renovation (American Institute of Architects and the Facilities Guidelines Institute, 2006, Centers for Disease Control and Prevention, 2003), while older facilities not undergoing renovation are advised to remain compliant with guidelines in existence at the time of original construction (CDC, 2003).

In September 2007, clinical personnel at Hospital A in Georgia noted an increase in invasive mold infections (IMIs), particularly mucormycosis, among patients with hematologic disorders. Hospital A and the Georgia Division of Public Health requested assistance from the CDC to determine the extent of the cluster, identify factors associated with mucormycosis, and develop recommendations to prevent further infections.

Section snippets

Case definitions and identification

IMIs were defined according to criteria consistent with the European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria for proven and probable invasive fungal infection (De Pauw et al., 2008). Possible IMIs were not included. The IMI index date was defined as the date on which the first IMI diagnostic specimen was collected.

A case-patient was defined as a hematology service patient with laboratory-confirmed mucormycosis diagnosed from January 1, 2006 to

IMIs at hospital A

Thirty-seven IMIs in 34 hematology service patients were identified from January 1, 2005, to September 30, 2007: aspergillosis (12 cases), mucormycosis (11), fusariosis (6), other mold infections (3), and unspecified mold infections (5) (Fig. 1A and B). During the same time period, there were 14 IMIs in non-hematology service patients; 4 of these were mucormycosis cases (Fig. 2).

Mucormycosis case-patients

We identified 15 mucormycosis cases in hematology patients from January 1, 2003, to September 30, 2007 (Fig. 3).

Discussion

We investigated a mucormycosis cluster in Hospital A patients with hematologic disorders. The 11 cases diagnosed from January 1, 2006, to October 31, 2007, represented a deviation from Hospital A's usual number of cases during a time when the number of hematology unit and service inpatient days increased only slightly. Although mucormycosis is a recognized complication of the immunosuppression experienced by acute leukemia patients and allogeneic HSCT recipients, it remains a sporadic, uncommon

Acknowledgments

We thank Jessica Possehn, CDC Epidemiology Elective medical student with the Office of Workforce and Career Development, for her assistance with data collection. We also thank the staff of the following Hospital A departments for their assistance in multiple aspects of this investigation: Infection Control, Hematology and Medical Oncology, Pathology and Laboratory Medicine, and Information Systems. We acknowledge Professor Sybren de Hoog and Dr. Grit Walther of the Centraalbureau voor

References (32)

  • Centers for Disease Control and Prevention (CDC)

    Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC)

    MMWR Recomm Rep

    (2003)
  • ChengVC et al.

    Outbreak of intestinal infection due to Rhizopus microsporus

    J Clin Microbiol

    (2009)
  • CourtneyR et al.

    Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults

    Br J Clin Pharmacol

    (2004)
  • De PauwB et al.

    Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

    Clin Infect Dis

    (2008)
  • GreenbergRN et al.

    Posaconazole as salvage therapy for zygomycosis

    Antimicrob Agents Chemother

    (2006)
  • ImhofA et al.

    Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole

    Clin Infect Dis

    (2004)
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    Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.

    ☆☆

    Presented in abstract form: 57th Annual Epidemic Intelligence Service Conference, Atlanta, GA. April 14–18, 2008 (Poster 23); and Focus on Fungal Infections 18, San Antonio, TX, March 5–7, 2008 (Abstract P-0023).

    Financial support. Office of Workforce and Career Development, Centers for Disease Control and Prevention.

    ★★

    Potential conflicts of interest: A.A.L. has served on advisory boards for Schering-Plough and has participated in clinical research trials sponsored by Schering-Plough and Astellas. G.M.L. has received research support from Astellas, Merck, and Pfizer; has received honoraria from Astellas, Schering-Plough, and Wyeth; and has consulted for Astellas and Merck. S.S.M. consulted for and received grant support from Pfizer and received an honorarium from Astellas, before commencing employment at the Centers for Disease Control and Prevention. All other authors: no conflict.

    1

    Current affiliation: Division of Sexually Transmitted Disease Prevention, Centers for Disease Control and Prevention, Atlanta, GA.

    2

    Current affiliation: ID Consultants, 6115 Powers Blvd., Suite 205, Parma, OH 44129, USA.

    3

    Current affiliation: Division of Global Disease Detection and Emergency Response, Centers for Disease Control and Prevention.

    4

    Current affiliation: Global Immunization Division, Centers for Disease Control and Prevention.

    5

    Current affiliation: Guest Researcher, Mycotic Diseases Branch, Centers for Disease Control and Prevention.

    6

    Current affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention.

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