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Table 1.  

Characteristic Heart transplant, n = 16 Lung transplant, n = 7 p value All patients, n = 23
Median age at Nocardia diagnosis, y (range) 61 (38–71) 59 (50–70) 0.98 61 (38–71)
Sex
   M 10 (62.5) 5 (71.4) 0.68 15 (65.2)
   F 6 (37.5) 2 (28.6) 0.68 8 (34.8)
Median no. months from transplant to Nocardia diagnosis (range) 4.8 (3–19) 22.8 (5–263) <0.01 6.3 (3–263)
CMV, donor positive/recipient negative 4 (25.0) 0 0.17 4 (17.4)
Episodes of organ rejection from date of transplant to diagnosis of Nocardia
   Any grade† 16 (100) 3 (42.9) <0.01 19 (82.6)
   <2R/A3 6 (37.5) 3 (42.9) 0.81 9 (39.1)
   ≥2R/A3 10 (62.5) 0 <0.01 10 (43.4)
Diabetic at time of diagnosis 13 (81.3) 2 (28.6) <0.01 15 (65.2)
Received intravenous immunoglobulin therapy 7 (43.8) 6 (85.7) 0.06 13 (56.5)
Respiratory virus ≤6 mo before Nocardia 9 (56.3) 6 (85.7) 0.17 15 (65.2)
CMV DNA detected by PCR ≤6 mo before Nocardia 6 (37.5)‡ 1 (14.3)§ 0.27 7 (30.4)
Significant CMV viremia ≤6 mo before Nocardia¶ 4 (25.0) 1 (14.3) 0.57 5 (21.7)
Medications received
   Sulfamethoxazole/trimethoprim prophylaxis 13 (81.3) 7 (100) 0.22 20 (87.0)
   Azithromycin prophylaxis 1 (6.3) 7 (100) <0.01 8 (34.8)
   Induction with basiliximab 16 (100) 2/5 (40.0) <0.01 18/21 (85.7)
   Tacrolimus immunosuppression 16 (100) 7 (100) 1 23 (100)
   Mycophenolic acid immunosuppression 16 (100) 5/5 (100) 1 21/21 (100)
   Prednisone immunosuppression 16 (100) 5/5 (100) 1 21/21 (100)

Table 1. Clinical characteristics of heart and lung transplant recipients with confirmed Nocardia infection, Greater Sydney, New South Wales, Australia, June 2015–March 2021*

*Values are no. (%) patients except as indicated. Denominators are indicated for categories in which only some patients had data available. CMV, cytomegalovirus.
†Defined as ≥1R on endomyocardial biopsy for heart transplant rejections and ≥A1 on bronchial biopsy for lung transplant rejections in accordance with International Society of Heart and Lung Transplantation 2004 and 2007 grading guidelines.
‡Among heart transplant recipients, the highest CMV PCR values (IU/mL) included: 1,169 copies 3 mo before Nocardia diagnosis; 16,271 4 mo before Nocardia diagnosis; 4,446 3 mo before Nocardia diagnosis; 27,1942 within a month before Nocardia diagnosis; 324 within a month before Nocardia diagnosis; and 103 within 1 month before Nocardia diagnosis.
§The highest CMV PCR value (IU/mL) was 1,240 within a month before Nocardia diagnosis.
¶Defined as CMV PCR copies >1,000 IU/mL.

Table 2.  

Nocardia species Heart transplant, n = 16 Lung transplant, n = 7 p value All patients, n = 23
N. abscessus 0 1 (14) 0.12 1 (4)
N. beijingensis 1 (6) 0 0.50 1 (4)
N. cyriacigeorgica 2 (13) 0 0.33 2 (9)
N. exalbida 0 1 (14) 0.12 1 (4)
N. farcinica 4 (25) 2 (29) 0.85 6 (26)
N. fluminea 1 (6) 0 0.50 1 (4)
N. nova 6 (38) 2 (29) 0.68 8 (35)
N. veterana 2 (13) 1 (14) 0.91 3 (13)

Table 2. Comparison of Nocardia species infecting heart and lung transplant recipients, Greater Sydney, New South Wales, Australia, June 2015–March 2021*

*Values are no. (%) patients except as indicated.

Table 3.  

Drug Heart transplant, n = 16 Lung transplant, n = 7 p value All patients, n = 23
Amikacin 16 (100) 7 (100) Referent 23 (100)
Augmentin 0 0/6 Referent 0/22 (0)
Cefepime 1/15 (6.7) 3/6 (50.0) 0.02 4/21 (19.0)
Ceftriaxone 3 (18.8) 4 (57.1) 0.07 7 (30.4)
Ciprofloxacin 4 (25.0) 1 (14.3) 0.57 5 (21.7)
Clarithromycin 10 (62.5) 4 (57.1) 0.81 14 (60.9)
Doxycycline 1/15 (6.7) 2 (28.6) 0.16 3/22 (13.6)
Imipenem 7 (43.8) 3 (42.9) 0.97 10 (43.5)
Linezolid 16 (100) 7 (100) Referent 23 (100)
Minocycline 1 (6.3) 2 (28.6) 0.14 3 (13.0)
Moxifloxacin 4 (25.0) 1/6 (16.7) 0.68 5/22 (22.7)
Tobramycin 4 (25.0) 2/6 (33.3) 0.70 6/22 (27.3)]
Sulfamethoxazole/trimethoprim 15 (93.8) 7 (100) 0.50 22 (95.7)

Table 3. Comparison of the number and proportion of Nocardia isolates susceptible to select antimicrobial drugs between heart and lung transplant recipients, Greater Sydney, New South Wales, Australia, June 2015–March 2021*

*Values are no. (%) patients except as indicated. Denominators are indicated for categories in which only some patients had data available.

Table 4.  

Characteristic Preoutbreak, Jun 2015–Dec 2017 Outbreak,
Postoutbreak
p value
Nocardia cases/mo 0.16 0.46 0.07  
Average monthly precipitation, mm/mo 60.4 40.0 103.2 <0.01
Average monthly temperature °C 17.0 17.8 17.8 0.79
Average monthly dryness* 0.4 0.3 0.5 <0.01
Average monthly windspeed, m/s 1.0 0.9 1.0 0.62
Average monthly erodibility† 0.1 0.2 0.1 0.26

Table 4. Climate conditions and Nocardia incidence before, during, and after a Nocardia outbreak among heart and lung transplant recipients, Greater Sydney, New South Wales, Australia, January 2018–December 2019*

*Ratio of evaporation to potential evaporation, such that 0.0 is perfectly dry and 1.0 is perfectly wet.
†Calculated by the formula (1 – dryness) × windspeed

Table 5.  

Climate conditions Monthly average with no Nocardia cases, n = 73 Monthly average with confirmed Nocardia cases, n = 17 p value All months, n = 90
Precipitation, mm/mo 66.3 63.3 0.42 65.7
Dryness 0.4 0.3 <0.01 0.4
Temperature, °C 17.4 18.9 0.24 17.7
Windspeed, m/s 1.0 1.1 0.37 1.0
Normalized windspeed, m/s 0.2 0.4 <0.01 0.2
Normalized erodibility, m/s 0.1 0.4 <0.01 0.2

Table 5. Comparison of climate conditions during months with and without Nocardia infections, Greater Sydney, New South Wales, Australia, June 2015–March 2021

CME / ABIM MOC

Multispecies Outbreak of Nocardia Infections in Heart Transplant Recipients and Association With Climate Conditions, Australia

  • Authors: Jonathan Li, MD; Cindy Lau, BPharm; Naomi Anderson, RN; Fay Burrows, GradDipPharmPrac; Feras Mirdad, MBBS; Lilibeth Carlos, BPharm; Andrew Pitman, PhD; Kavitha Muthiah, MBChB, PhD; David R. Darley, MBBS; David Andresen, MBBS; Peter Macdonald, MBBS, PhD; Deborah Marriott, MBBS, PhD; Nila J. Dharan, MD, PhD
  • CME / ABIM MOC Released: 10/21/2022
  • Valid for credit through: 10/21/2023, 11:59 PM EST
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, transplant clinicians, cardiologists, public health officials, epidemiologists, and other clinicians caring for heart transplant recipients who may be at increased risk for Nocardia infections.

The goal of this activity is for learners to be better able to describe clinical factors and climate conditions in an outbreak of Nocardia infections in heart transplant recipients at St Vincent's Hospital, Sydney, Australia, in 2018-2019 and to compare heart transplant recipients and lung transplant recipients diagnosed with Nocardia infections from June 2015 to March 2021 in Sydney, Australia, based on a retrospective review.

Upon completion of this activity, participants will:

  • Compare patient demographic characteristics, host risk factors (underlying medical conditions, rejection rates, immunosuppressive regimens), and antimicrobial prophylaxis regimens in heart transplant recipients and lung transplant recipients with Nocardia infections, based on a retrospective review of an outbreak of Nocardia infections in heart transplant recipients at St Vincent's Hospital, Australia, between 2018 and 2019
  • Assess climate characteristics during the time of the outbreak of Nocardia infections in heart transplant recipients at St Vincent's Hospital, Australia between 2018 and 2019, based on a retrospective review
  • Evaluate clinical and public health implications of clinical factors and climate conditions in an outbreak of Nocardia infections in heart transplant recipients at St Vincent's Hospital, Australia between 2018 and 2019, based on a retrospective review


Disclosures

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Faculty

  • Jonathan Li, MD

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia

  • Cindy Lau, BPharm

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia
    School of Pharmacy
    Faculty of Medicine and Health
    University of Sydney
    Sydney, Australia

  • Naomi Anderson, RN

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia

  • Fay Burrows, GradDipPharmPrac

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia

  • Feras Mirdad, MBBS

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia

  • Lilibeth Carlos, BPharm

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia

  • Andrew Pitman, PhD

    Australian Research Council Centre of Excellence for Climate Extremes and Climate Change Research Centre
    University of New South Wales Sydney
    Sydney, New South Wales, Australia

  • Kavitha Muthiah, MBChB, PhD

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia
    Victor Chang Cardiac Research Institute
    Darlinghurst, New South Wales, Australia

  • David R. Darley, MBBS

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia
    University of New South Wales Medicine
    St Vincent's Clinical School
    University of New South Wales Sydney
    Sydney, New South Wales, Australia

  • David Andresen, MBBS

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia
    University of Notre Dame
    Sydney, New South Wales, Australia

  • Peter Macdonald, MBBS, PhD

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia
    Victor Chang
    Cardiac Research Institute
    Darlinghurst, New South Wales, Australia

  • Deborah Marriott, MBBS, PhD

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia

  • Nila J. Dharan, MD, PhD

    St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales, Australia
    Kirby Institute
    University of New South Wales Sydney
    Sydney, New South Wales, Australia

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie Inc.

Editor

  • Dana C. Dolan, BS

    Copyeditor
    Emerging Infectious Diseases

Compliance Reviewer

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.


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CME / ABIM MOC

Multispecies Outbreak of Nocardia Infections in Heart Transplant Recipients and Association With Climate Conditions, Australia

Authors: Jonathan Li, MD; Cindy Lau, BPharm; Naomi Anderson, RN; Fay Burrows, GradDipPharmPrac; Feras Mirdad, MBBS; Lilibeth Carlos, BPharm; Andrew Pitman, PhD; Kavitha Muthiah, MBChB, PhD; David R. Darley, MBBS; David Andresen, MBBS; Peter Macdonald, MBBS, PhD; Deborah Marriott, MBBS, PhD; Nila J. Dharan, MD, PhDFaculty and Disclosures

CME / ABIM MOC Released: 10/21/2022

Valid for credit through: 10/21/2023, 11:59 PM EST

processing....

Abstract and Introduction

Abstract

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018–2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015–March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018–2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018–2019, may explain this outbreak of Nocardia infections in HTR.

Introduction

Nocardia is an environmental aerobic actinobacterium (Actinomycete) that stains positive on Gram stain and forms commonly in soil and water. Infection is primarily acquired through inhalation; however, it may also occur through direct inoculation into the skin or via ingestion of the microorganism[1,2]. Depending on the route of infection, clinical manifestations may include pulmonary, cutaneous, intravenous line infections, and disseminated disease, which frequently involves the nervous system and skeletal or soft-tissue structures[1,2]. Noncutaneous disease is most commonly reported in immunocompromised persons such as solid organ transplant recipients; recent studies showed the greatest risk is among lung transplant recipients (LTR, 3.5%) followed by heart transplant recipients (HTR, 2.5%)[3]. Treatment in immunocompromised patients is generally for a minimum period of 6 months. Nocardiosis in solid organ transplant recipients is associated with a 10-fold increase in 1-year mortality rate (16.2%, compared with 1.3% in recipients without nocardiosis)[4].

In January 2018, an increased rate of Nocardia infections was noted among HTR at St Vincent’s Hospital in Sydney, New South Wales (NSW), Australia, but not among LTR who underwent transplants during the same timeframe. The rise in Nocardia infections coincided with a period of extreme weather conditions in NSW; 2018 was the second warmest and seventh driest year, and 2019 was the warmest and driest year on record in NSW[5,6]. Similar extreme weather patterns were experienced across the rest of Australia[7,8]. Previous studies have observed that Nocardia infections occur more frequently in dry and windy climates, such as that of the Southwest region of the United States[1,9]. Such climate conditions are thought to increase aerosolization of Nocardia organisms from soil, increasing the possibility of inhalation and therefore subsequent infection[1,9,10].

We report an outbreak of Nocardia infections in HTR at St Vincent’s Hospital during January 2018–August 2019. Because Nocardia infections in LTR did not increase during that period, we sought to compare patient demographic characteristics, host risk factors (underlying medical conditions, rejection rates, immunosuppressive regimens), and antimicrobial prophylaxis regimens for HTR and LTR. In addition, because Nocardia is an environmental organism and the outbreak occurred during some of the driest years recorded in Australia, we sought to characterize climate characteristics during the time of the outbreak[7,8]. St Vincent’s Hospital Human Research Ethics Committee reviewed and approved the study.