Monday, March 27, 2023
| 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.
| 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.
| 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.
| 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
| 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
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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.
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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.
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.
