This observational, retrospective, cross-sectional study included 211 patients admitted to 3 tertiary health centers in Ipatinga and Belo Horizonte in the state of Minas Gerais, Brazil, between 2003 and 2017. An initial survey of medical records containing International Classification of Diseases related to IE (ICD 10 I33.0) was conducted. These records were analyzed and information on epidemiological, microbiological, valvular, and outcome characteristics were collected in an Excel database.

The inclusion criterion was definite or probable IE according to the modified Duke criteria.⁷ Patients whose medical records were incomplete, who were transferred during hospitalization, or who were still hospitalized at the time of analysis were excluded. After selection, data from the medical records were collected, including age, sex, blood culture, and prognosis. The microbiology was determined through blood culture results, and the location of the IE was determined through echocardiographic or perioperative findings.

This study was approved by the ethics committee of the Faculty of Medical Sciences of Minas Gerais (CAAE 60893616.7.0000.5134). Informed consent was not required due to the retrospective nature of the study.

Categorical variables are presented as absolute and relative frequencies, and quantitative variables are presented as median (1^st – 3^rd quartile). The normality of quantitative variables was assessed using the Shapiro-Wilk test, while the Wilcoxon-Mann-Whitney test was used to compare quantitative variables among groups. The association between categorical variables was assessed using the chi-square test and Fisher's exact test. Binary logistic models were constructed to verify the association with mortality, and the results are presented as odds ratios (OR) and 95% confidence intervals. The Mann- Kendall test was used to verify the temporal trend. The analysis was performed in R version 3.5.2, with p <0.05 considered significant.

Overall mortality was 22.3%. It was observed that increasing age is a risk factor for death (p = 0.028). However, when the sample was stratified into patients younger and older than 65 years of age, there was no statistical relevance ( Table 2 ). Among patients younger than 65 years who died, the native aortic valve was the most affected site (33.3%) and Staphylococcus spp. was the most frequent pathogen, representing 30.6% of the cases. Regarding the 11 deaths in patients older than 65 years, most were due to Streptococcus spp., and the most prevalent location was the native mitral valve. Sex, blood culture findings, and lesion location had no statistical relevance on mortality. Mortality from IE remained stable between 2003 and 2017 (τ = 0.010). The highest and lowest death rates occurred in 2004 and 2012, respectively.

Table 2

Characteristic	Death		OR (CI 95%)	p-value
	No (n=164)	Yes (n=47)
Sex
Male	117 (71.3%)	32 (68.1%)	-	-
Female	47 (28.7%)	15 (31.9%)	1.167 (0.568; 2.323)	0.611
Age (years) (median [1st - 3rd quartile])	46.00 (31-59)	52.00 (39-63)	1.020 (1.003; 1.039)	0.028
<65	137 (83.5%)	36 (76.6%)	-	-
65 or more	27 (16.5%)	11 (23.4%)	1.550 (0.263; 3.358)	0.277
Blood culture findings
Staphylococcus spp.	28 (17.1%)	12 (25.5%)	1.665 (0.750; 3.548)	0.195
Staphylococcus aureus	15 (9.1%)	6 (12.8%)	1.454 (0.493; 3.827)	0.467
Coagulase-negative Staphylococci	13 (7.9%)	6 (12.8%)	1.700 (0.568; 4.590)	0.311
Streptococcus spp.	26 (15.9%)	5 (10.6%)	0.632 (0.204; 1.625)	0.377
Enterococcus spp.	9 (5.5%)	5 (10.6%)	2.050 (0.603; 6.268)	0.219
Other*	10 (6.1%)	-	-	-
Not specified	11 (6.7%)	3 (6.4%)	0.948 (0.208; 3.197)	0.937
Negative blood culture	59 (36%)	12 (25.5%)	0.610 (0.285; 1.237)	0.184
Location
Native valves†	114 (69.5%)	35 (74.5%)	1.279 (0.627; 2.756)	0.511
Mitral	70 (42.7%)	18 (38.3%)	0.833 (0.423; 1.609)	0.591
Aortic	43 (26.2%)	13 (27.7%)	1.076 (0.506; 2.190)	0.844
Tricuspid	15 (9.1%)	6 (12.8%)	1.454 (0.493; 3.827)	0.467
Pulmonary	2 (1.2%)	1 (2.1%)	1.761 (0.081; 18.779)	0.647
Prosthetic valves	40 (24.4%)	11 (23.4%)	0.947 (0.426; 1.985)	0.889
Pacemaker cable	7 (4.3%)	2 (4.3%)	0.997 (0.145; 4.297)	0.997
Other‡	5 (3%)	1 (2.1%)	0.691 (0.036; 4.428)	0.739
Unidentified location	3 (1.8%)	-	-	-

* Candida spp., Proteus mirabilis, Proteus penneri, E. coli, Enterobacter sp., Klebsiella sp., Achromobacter xylosoxidans, Morganella morganii, Stenotrophomonas maltophilia, Facklamia hominis. OR: odds ratio. † Some patients had lesions in more than one place. ‡ Right atrium, pulmonary arteries, ostium of the interventricular defect, ostium of superior vena cava. P-value refers to the logistic regression model.

Of the 211 patients, 149 were men and 62 were women. A total of 82.3% of the men and 81.9% of the women diagnosed with IE were younger than 65 years of age (no significant difference). Native valves were most affected, especially the mitral valve, regardless of the patient's sex, representing 40.3% of the infections in men and 45.2% in women, while the pulmonary valve was the least affected site. Of note, prosthetic valve endocarditis occurred in 22.8% and 27.4% of the men and women, respectively, at a ratio of approximately 1:3 in relation to native valves. The native aortic valve was significantly more affected in men than women (p = 0.017). There was no association between the other findings (blood culture, age group, and other IE sites) and sex.

Table 3 shows the relationship between microbiological findings, age, and affected valve. There was no association between a specific microorganism and age, with individuals younger or older than 65 being equally affected. Infection by atypical microorganisms was more common in patients with prosthetic valve endocarditis (p = 0.014). Individuals without mitral lesions were more prone to infection by Coagulase-negative Staphylococci (p = 0.026). Regarding the main pathogens found during the study period ( Figure 1 ), all had a non-significant trend according to the Mann Kendall test: Staphylococcus spp. (τ = 0.293, p = 0.148), Streptococcus spp. (τ = -0.078, p = 0.727) and negative blood culture (τ = -0.332, p = 0.100), which indicates that the occurrence of these microorganisms was stable over the years.

Table 3

Microorganism	Age (years)							Mitral valve affected					Aortic valve affected
	< 65 n=173		≥ 65 n=38			p-value		No n=123		Yes n=88	p-value		No n=155			Yes n=56	p-value
Staphylococcus spp.	32 (18.5%)	8 (21.1%)					0.892†	29 (23.6%)	11 (12.5%)		0.065†		29 (18.7%)	11 (19.6%)			1.000†
Staphylococcus aureus	18 (10.4%)	3 (7.9%)					0.773‡	13 (10.6%)	8 (9.1%)		0.904†		18 (11.6%)	3 (5.4%)			0.296‡
Coagulase-negative Staphylococci	14 (8.1%)	5 (13.2%)					0.348‡	16 (13%)	3 (3.4%)		0.026‡		11 (7.1%)	8 (14.3%)			0.181†
Streptococcus spp.	25 (14.5%)	6 (15.8%)					1.000†	18 (14.6%)	13 (14.8%)		1.000†		22 (14.2%)	9 (16.1%)			0.905†
Enterococcus spp.	10 (5.8%)	4 (10.5%)					0.286‡	7 (5.7%)	7 (8%)		0.581‡		9 (5.8%)	5 (8.9%)			0.531‡
Other*	7 (4%)	3 (7.9%)					0.391‡	8 (6.5%)	2 (2.3%)		0.199‡		8 (5.2%)	2 (3.6%)			1.000‡
Not specified	10 (5.8%)	4 (10.5%)					0.286‡	10 (8.1%)	4 (4.5%)		0.404‡		9 (5.8%)	5 (8.9%)			0.531‡
Negative blood culture	61 (35.3%)	10 (26.3%)					0.386†	35 (28.5%)	36 (40.9%)		0.082†		53 (34.2%)	18 (32.1%)			0.910†
	Tricuspid valve affected									Prosthetic valves affected
Microorganism	No n=190			Yes n=21				p-value		No n=160			Yes n=51			p-value
Staphylococcus spp.	33 (17.4%)			7 (33.3%)				0.139†		31 (19.4%)			9 (17.6%)			0.945†
Staphylococcus Aureus	17 (8.9%)			4 (19%)				0.140‡		17 (10.6%)			4 (7.8%)			0.789†
Coagulase-negative Staphylococci	16 (8.4%)			3 (14.3%)				0.413‡		14 (8.8%)			5 (9.8%)			0.784‡
Streptococcus spp.	29 (15.3%)			2 (9.5%)				0.746‡		25 (15.6%)			6 (11.8%)			0.652†
Enterococcus spp.	12 (6.3%)			2 (9.5%)				0.636‡		10 (6.2%)			4 (7.8%)			0.748‡
Other*	10 (5.3%)			-				-		4 (2.5%)			6 (11.8%)			0.014‡
Not specified	13 (6.8%)			1 (4.8%)				1.000‡		9 (5.6%)			5 (9.8%)			0.334‡
Negative blood culture	62 (32.6%)			9 (42.9%)				0.485†		56 (35%)			15 (29.4%)			0.572†

* Candida spp., Proteus mirabilis, Proteus penneri, E. coli, Enterobacter sp., Klebsiella sp., Achromobacter xylosoxidans, Morganella morganii, Stenotrophomonas maltophilia, Facklamia hominis. † Chi-square test. ‡ Fisher’s exact test.

Figure 1

Our study is not without limitations. First, since we performed a retrospective analysis, associations between variables do not necessarily indicate a causal relationship. Second, the sample can be considered small, since we dealt with cases over 15 years at three different centers, as well as the fact that it included many probable IE cases (93 out of 211). However, few studies have been published on the epidemiological profile of Brazilian patients and, to the best of our knowledge, our study involves the largest such sample. It should also be pointed out that most of the probable IE cases involved a negative blood culture, which is related to the use of antibiotics. Third, no data on comorbidity, heart valve disorder, hemodynamic variables, heart failure, abscess formation, or heart valve surgery were collected. Thus, any discussion of mortality must be extremely limited. Finally, it was not possible to collect blood samples for blood culture in 34 patients, either because they received treatment prior to collection or because they began antibiotic therapy before being transferred to tertiary centers.