Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis

Figures & data

Table 1 Study Inclusion/Exclusion Criteria

	Inclusion Criteria	Exclusion Criteria
Population	Adults (aged ≥18 years) with IA or IM	Superficial/cutaneous or otherwise localized fungal infections Children (aged ≤17 years) with IMI
Interventions	Any treatment used in mold infection therapy	Prophylactic treatment with mold infection treatment
Comparators	Any or none	N/A
Outcomes	Risk factors and/or comorbidities associated with IMI	Non-included outcomes Outcomes not stratified by mold vs yeast infections
Study design	Observational studies: Prospective or retrospective Database analyses/registries Clinical trials Professional society guidelines Systematic literature reviews/meta-analyses (for study identification purposes only)	Observational Non-systematic reviews Case series/case reports Commentary/editorial letter
Setting	Inpatient and outpatient	N/A
Publication type	Manuscripts published in medical or economic journals indexed in MEDLINE/Embase Conference abstracts from 4 conferences: Congress of the European Hematology Association (EHA) American Society of Hematology (ASH) Trends in Medical Mycology (TIMM) European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)	Non-included publication types
Language	English	Non-English
Publication date	Full-text articles: published January 1, 2008 to October 2019 Conference abstracts: published January 1, 2015 to October 2019	Published prior to January 1, 2008
Other	Human subjects	Preclinical/animal subjects

Abbreviations: IA, Invasive Aspergillosis; IM, Invasive Mucormycosis; IMI, Invasive mold infection; N/A, Not applicable.

Figure 1 PRISMA Flow Diagram.

Table 2 Comorbidities Proportions Across IMI Studies in the SLR

Comorbidity/Risk Factor (46 Studies)	IA (n=35)	IM (n=11)
Healthy	2	2
Diabetes	17	8
Lung Disease	10	2
Hematology Malignancy or Disease	17	7
Solid Organ Transplant	11	4
Heart Disease	9	0
Liver Disease	7	2
Renal Impairment	7	3
Immuno-compromised	8	4
Hematologic transplant	6	1
Solid Malignancy	7	3

Abbreviations: IA, Invasive Aspergillosis; IM, Invasive Mucormycosis; IMI, Invasive mold infection; SLR, Systematic literature review.

Table 3 Weighted Average Prevalence of Comorbidities Across IMI Patients in the SLR

Comorbidity/Risk Factor (46 Studies)	IA	IM
Healthy	15.0%	11.0%
Diabetes	19.0%	37.0%
Lung Disease	46.0%	12.0%
Hematology Malignancy or Disease	48.0%	41.0%
Solid Organ Transplant	56.0%	71.0%
Heart Disease	51.0%	NR
Liver Disease	38.0%	3.0%
Renal Impairment	23.0%	18.0%
Immuno-compromised	7.0%	58.0%
Hematologic transplant	4.0%	35.0%
Solid Malignancy	10.0%	2.0%

Abbreviations: IA, Invasive Aspergillosis; IM, Invasive Mucormycosis; IMI, Invasive mold infection; NR, Not reported; SLR, Systematic literature review.

Table 4 Rates of Invasive Mold Infections in Comorbidity and Risk Factor Groups

Evaluation Group	N	Invasive Aspergillosis n (%)*	Invasive Mucormycosis n (%)*	Co-Infected n (%)*
Diabetes	5,730,144	23,578 (0.41%)	2257 (0.04%)	117 (0.003%)
Lung Disease	9,095,448	42,939 (0.47%)	3264 (0.04%)	204 (0.002%)
Cystic fibrosis	19,030	1000 (5.25%)	12 (0.06%)	3 (0.02%)
Tuberculosis	40,788	599 (1.47%)	30 (0.07%)	4 (0.01%)
COPD	9,063,186	42,719 (0.47%)	3255 (0.04%)	0 (0.00%)
HEM/ONC	962,428	10,638 (1.11%)	1133 (0.12%)	161 (0.02%)
AML	34,367	1562 (4.55%)	145 (0.42%)	66 (0.19%)
Lymphoma	209,953	2242 (1.07%)	165 (0.08%)	40 (0.02%)
Leukemia	126,982	2354 (1.85%)	208 (0.16%)	81 (0.06%)
Other	148,458	1133 (0.76%)	102 (0.07%)	25 (0.02%)
Stem Cell	21,463	1065 (4.96%)	106 (0.49%)	42 (0.20%)
Neutropenia	278,390	4299 (1.54%)	332 (0.12%)	113 (0.04%)
SOT	125,381	2536 (2.02%)	144 (0.11%)	41 (0.03%)
Kidney transplant	77,315	1097 (1.42%)	61 (0.08%)	14 (0.02%)
Heart transplant	14,294	423 (2.96%)	33 (0.23%)	9 (0.06%)
Lung transplant	9171	991 (10.81%)	39 (0.43%)	18 (0.20%)
Liver transplant	32,456	760 (2.34%)	38 (0.12%)	7 (0.02%)
Pancreas transplant	6268	155 (2.47%)	10 (0.16%)	3 (0.05%)
Heart and Lung transplant	33	6 (18.18%)	0 (0.00%)	0 (0.00%)
Pancreas and Kidney transplant	53	0 (0.00%)	0 (0.00%)	0 (0.00%)
Intestine transplant	959	86 (8.97%)	8 (0.83%)	2 (0.21%)
Other transplant	5606	132 (2.35%)	8 (0.14%)	3 (0.05%)

Note: *Percent of evaluation cohort.

Abbreviations: AML, Acute Myeloid Leukemia; COPD, chronic obstructive pulmonary disorder; HEM/ONC, hematology and oncology; N, number of patients; SOT, Solid Organ Transplant.

Table 5 Mean Post-Index CCI Score in Diabetes, Lung Disease, SOT, and HEM/ONC Diagnosed Patients by IMI-Status

Cohort	Entire Cohort	Invasive Aspergillosis Mean ± SD Diff (95% CI)^† p-value	Invasive Mucormycosis Mean ± SD Diff (95% CI)^† p-value	Co-infected Mean ± SD Diff (95% CI)† p-value
Diabetes	2.28 ± 1.86*	3.16 ± 2.44 0.88 (0.86, 0.9) <0.0001	2.55 ± 2.05 0.27 (0.19, 0.35) <0.0001	3.68 ± 2.57 1.40 (1.13, 1.67) <0.0001
Lung Disease	1.90 ± 1.75*	2.68 ± 2.32 0.78 (0.76, 0.80) <0.0001	2.98 ± 2.18 1.08 (1.02, 1.14) <0.0001	3.85 ± 2.61 1.95 (1.71, 2.19) <0.0001
HEM/ONC	2.99 ± 2.61*	3.70 ± 2.55 0.71 (0.66, 0.76) <0.0001	3.52 ± 2.11 0.53 (0.38, 0.68) <0.0001	4.14 ± 2.49 1.15 (0.75, 1.55) <0.0001
SOT	3.26 ± 2.28*	4.00 ± 2.83 0.74 (0.65, 0.83) <0.0001	4.70 ± 2.67 1.44 (1.07, 1.81) <0.0001	4.88 ± 2.79 1.62 (0.92, 2.32) <0.0001

Notes: *Represents Mean CCI score for Total cohort, including IMI patients. †Difference relative to mean CCI score of Total cohort.

Abbreviations: CCI, Charlson Comorbidity Index; Diff, Difference; HEM/ONC, hematology and oncology; IMI, Invasive mold infection; SD, Standard deviation; SOT, Solid Organ Transplant.

Table 6 Frequencies of Common Metabolic Comorbidities by Cohort and Type of Infection

Cohort	Total (%)*	Invasive Aspergillosis (%)*	Invasive Mucormycosis (%)*
Diabetes
Essential hypertension	28–45	38–55	56–72
Hyperlipidemia	18–36	25	42
Lung Disease
Essential hypertension	12–25	27–36	50–62
Hyperlipidemia	11	18	32–36
HEM/ONC
Essential hypertension	25	28–34	41–50
Hyperlipidemia	15–18	16	28–29
SOT
Diabetes	12	NR	28–33
Essential hypertension	28	38	48
Hyperlipidemia	15–22	22	30

Notes: *Represents frequencies of top ICD-9/ICD-10 codes reported for patient cohort >20%; ranges reflect differences in codes.

Abbreviations: HEM/ONC, hematology and oncology; SOT, Solid Organ Transplant; NR, Not reported.