Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic malignancies at a large comprehensive cancer center

Abstract

Background: Invasive Mucorales infections (IMI) lead to significant morbidity and mortality in immunocompromised hosts. The role of season and climatic conditions in case clustering of IMI remain poorly understood.

Methods: Following detection of a cluster of sinopulmonary IMIs in patients with hematologic malignancies, we reviewed center-based medical records of all patients with IMIs and other invasive fungal infections (IFIs) between January of 2012 and August of 2015 to assess for case clustering in relation to seasonality.

Results: A cluster of 7 patients were identified with sinopulmonary IMIs (Rhizopus microsporus/azygosporus, 6; Rhizomucor pusillus, 1) during a 3 month period between June and August of 2014. All patients died or were discharged to hospice. The cluster was managed with institution of standardized posaconazole prophylaxis to high-risk patients and patient use of N-95 masks when outside of protected areas on the inpatient service. Review of an earlier study period identified 11 patients with IMIs of varying species over the preceding 29 months without evidence of clustering. There were 9 total IMIs in the later study period (12 month post-initial cluster) with 5 additional cases in the summer months, again suggesting seasonal clustering. Extensive environmental sampling did not reveal a source of mold. Using local climatological data abstracted from National Centers for Environmental Information the clusters appeared to be associated with high temperatures and low precipitation.

Conclusions: Sinopulmonary Mucorales clusters at our center had a seasonal variation which appeared to be related to temperature and precipitation. Given the significant mortality associated with IMIs, local climatic conditions may need to be considered when considering center specific fungal prevention and prophylaxis strategies for high-risk patients.

Keywords: Climate; Fungus; Healthcare-associated infections; Immunocompromised host; Mold; Mucormycosis; Seasonal.

Fig. 1

Red areas indicate the locations of patients involved in the first Mucorales cluster (n = 7). Floor plans indicate locations of individual patients over the study period of June–August 2014 in red. a. The leukemia unit. Since patients were admitted multiple times over the period of interest into multiple rooms, rooms noted in red are greater than the number of patients in cluster. No specific rooms were identified to be associated with cases. Stars indicate rooms that were designated as negative pressure rooms. Only one patient was placed into a negative pressure room during the period of interest. b. The hematopoietic cell transplant unit. Areas of involvement (red) include intensive care unit rooms, and the blue star indicates the negative pressure rooms. Patients in these rooms were moved to these areas after symptom onset. Only one other room was linked to this episode and included the autologous transplant recipient treated during the study period on this floor; this patient had also spent time on the leukemia unit prior to admission on this floor

Fig. 2

Posaconazole use (prophylaxis and treatment) prior to and after the cluster among inpatient hematology/oncology patients. The grey bars indicate the total number of unique inpatients during each month admitted to inpatient hematology/oncology units. Blue bars indicate the number of patients on posaconazole during these periods. The yellow arrow indicates the starting point for post-cluster interventions. Comparing Sept 2013 through August 2014 and Sept 2014 through August 2015, use of posaconazole significantly increased (90/3614 [2.5%] vs. 575/3973 [14.5%], p < 0.001)

Fig. 3

Correlation between the rates of invasive Mucorales infections and local temperature and precipitation patterns* during the initial cluster period (June – August, 2014) and the periods before and after the cluster. *Mean monthly temperature and total monthly precipitation were used for these analyses. Incidence of Mucorales infections was significantly higher during months with mean temperature above 20 degrees C (IRR, 4.64; 95% CI 2.15–10.00; p < 0.001) and not significantly associated with monthly total precipitation (p = 0.86). Green bars indicate the initial cluster of cases. Local temperature and precipitation data were gathered from Seattle Sand Point Weather Service Forecast Office station using the following website: http://www.ncdc.noaa.gov/cdo-web/

Fig. 4

a/b: Heat map representing the locations of construction and demolition permits issued by the City of Seattle in calendar years 2014 and 2015. All data presented within 1 km of inpatient cancer units (University of Washington Medical Center [a] and the ambulatory clinic (Seattle Cancer Care Alliance [b]). Blue central dot indicates location of the facility