Incidence, clinical characteristics, and outcomes of nosocomial Enterococcus spp. bloodstream infections in a tertiary-care hospital in Beijing, China: a four-year retrospective study

Eligible patients included all patients aged ≥18 years with at least 1 positive blood culture for Enterococcus spp. In patients with persistent BSIs caused by the same organism, only the first episode was included. If the patients had 2 or more separate BSIs, each infection was considered individually. All patients were identified by searching the real-time nosocomial infection surveillance system (RT-NISS) [23]. This platform utilises data from electronic medical record systems, such as hospital stay, temperature changes, and microbiology results with the application of clinically validated algorithms to identify and classify all of the patients’ infections. RT-NISS was developed by the Infection Management and Disease Control Department of PLAGH.

The diagnosis of enterococcal BSI should meet the following criteria: 1)isolation of Enterococcus spp. from one or more blood cultures; and one of the following 2) fever (>38 °C), chills, or hypotension; and 3) eliminated the possibility of contamination during the collection and cultivation of blood samples [24]. Nosocomial BSI was defined as the first positive blood culture obtained ≥48 h after hospital admission and with no evidence of infection at admission [15, 24]. An episode was defined as the positive isolation of enterococcus from at least one blood culture sample from a patient and without the prior blood culture isolating the same bacteria within the previous 30 days [2, 25]. Onset of BSIs was defined as the date when the blood culture was collected. Polymicrobial BSIs were defined as 2 or more clinically important organisms isolated from 1 single blood culture sample or different blood culture samples within 48 h. Appropriate antimicrobial treatment was defined as an active antimicrobial choice and an adequate dosage within 5 days from the onset. Empirical antimicrobial therapy was defined as the antimicrobial agents given within 24 h after the onset of BSIs. Active agents were confirmed according to the antimicrobial susceptibility test.

Blood was cultured using BacT/ALERT 3D system (Becton-Dickinson, Sparks, MD, USA) in the microbiology laboratory. Species identification was performed using the VITEK 2 system (BioMérieux, Marcy 1′Étoile, France). Antibiotic susceptibility testing was performed using the VITEK 2 system or the Kirby-Bauer Disk Diffusion method (Oxoid, UK) according to the recommendations proposed by the Clinical and Laboratory Standards Institute (CLSI).

Categorical variables were expressed as frequency counts and percentages with 95% confidence interval (95% CI). Continuous variables were expressed as median and interquartile ranges (IQRs). Comparison of categorical variables was performed using Pearson’s chi-squared test or Fisher’s exact test, and comparison of continuous variables was performed using the Mann-Whitney U test. In order to identify the risk factors associated with mortality, a multivariate logistic regression model with backward method was generated to control the effects of confounding variables. Variables statistically related (p < 0.10) to mortality in the univariate logistic analyses were chosen to build the multivariate model. Results with a 2-tailed p-value < 0.05 were considered to be significant. All statistical analyses were run using SPSS 20.0 software (IBM Corp., Armonk, NY, USA).

For the remaining 226 episodes, classification was available in 224 (99%, 95% CI 98–100%). The most common Enterococcus species was E. faecium, which comprised 167 (74%, 95% CI 68–80%) of all episodes. E. faecalis was the second largest species, comprising 46 (20%, 95% CI 15–25%) of episodes. Of the remaining episodes, 6 (3%, 95% CI 1–5%) due to E. casseliflavus, 3 (1%, 95% CI 0–3%) due to E. gallinarum, and 2 (1%, 95% CI 0–3%) due to E. avium. The number of enterococci isolated in 2015 was the highest, and the least was in 2013. The species ratio in each year is shown in Fig. 1.

The overall incidence of nosocomial enterococcal BSIs was 3.9 episodes per 10,000 admissions and the rate fluctuated from 3.3 to 4.4 episodes per 10,000 admissions during the 4 years (3.7 in 2012, 3.3 in 2013, 4.1 in 2014, and 4.4 in 2015). The overall incidence rates of E. faecium and E. faecalis were 2.9 episodes and 0.8 episodes per 10,000 admissions, respectively. Incidence of E. faecalis BSI showed a rising trend, while that of E. faecium was on the decline, as shown in Fig. 2.

Demographics and clinical data were available for all these 226 incident episodes as shown in Table 1. The median age was 65 years (IQR, 54–75), and 142 (63%, 95% CI 56–69%) of the patients were male. The age distribution was right skewed, with the peak incidence in the 50–59 years group (Figure 3). Malignancy was the most common comorbidity (58%, 95% CI 51–64%), followed by cardiovascular disease (50%, 95% CI 43–57%) and pneumonia (33%, 95% CI 27–39%). The median and range of BMI were all within the normal range. The median CCI score was 3 (IQR, 2–6), and 86.7% of the patients had combined chronic diseases (CCI score ≥ 1). The median APACHE II score was 8 (IQR, 5–18). Some 172 (76%, 95% CI 71–82%) of the episodes occurred in the non-ICU ward, and 54 (24%, 95% CI 18–29%) occurred in the ICU. The median days of hospital stay prior to and after the onset of BSI were 15 and 18, respectively. A total of 210 (93%, 95% CI 90–96%) episodes had prior antibiotic exposure and 182 (81%, 95% CI 75–86%) had invasive medical procedures within the 30 days prior to BSI, such as a central intravenous catheter, Indwelling urinary catheter, and drainage tube.

A comparison of nosocomial BSIs according to E. faecium and E. faecalis in demographics and clinical characteristics is shown in Table 1. Patients with E. faecalis BSIs presented a higher BMI, but the median was in the normal range. Patients with E. faecium BSIs showed a higher CCI score than those with E. faecalis BSIs (median, 3 vs 2, p = 0.014). The median APACHE II score of patients with E. faecium BSIs was higher than in those with E. faecalis BSIs, but these were not statistically significant.

The source of nosocomial enterococcal BSIs was mainly related to intra-abdominal and central venous catheter, with the number of 92 (41%, 95% CI 34–47%) and 82 (36%, 95% CI 30–43%), respectively. Foci could not be confirmed for 65 (29%, 95% CI 23–35%) episodes. A total of 21 (9%, 95% CI 5–13%) episodes had polymicrobial infections.

The microbiological data of BSIs due to E. faecium and E. faecalis are presented in Table 2. There was no difference in the sources of BSI between these 2 species. Patients with E. faecium BSIs were more likely to have polymicrobial infections than those with E. faecalis (12% vs 2%, p = 0.048). No vancomycin-resistant E. faecalis isolate was found, and 7 (4%, 95% CI 1–7%) vancomycin- resistant E. faecium isolates were identified. E. faecium isolates had higher resistance rates than E. faecalis to ampicillin (86% vs 9%, p < 0.001), erythromycin (78% vs 56%, p = 0.009), and ciprofloxacin (86% vs 39%, p < 0.001).

Before obtaining the report of antibiotic susceptibility test reports, 98 (43%, 95% CI 37–50%) patients were treated with effective antibiotics. Patients with E. faecalis BSIs were more likely to get effective treatment by the empirical use of antibiotics (57% vs 37%, p = 0.018).

The median length of hospital stay was 34 days (IQR, 23–55). There was no statistical difference in the length of stay between patients with E. faecium BSIs (median, 35) and those with E. faecalis BSIs (median, 34). The total 7-day and 30-day mortality rates were 11% (95% CI 7–15%) and 24% (95% CI 18–29%), respectively. The 7-day and 30-day mortality rates for E. faecium BSIs were higher than E. faecalis BSIs (13% vs 9%, 25% vs 17%), but both had no statistical significance. Patients with malnutrition showed a higher risk of 7-day and 30-day mortality than patients with normal BMI.

Univariate analyses of predictors for 7-day mortality and 30-day mortality are shown separately in Table 3. The 7-day mortality was associated with pneumonia, impaired renal function, CCI, APACHE II score, ICU residence, prior exposure to immunosuppressive agents and central intravenous catheter, and appropriate empirical antimicrobial treatment. The predictors for 30-day mortality were similar to those for 7-day mortality, except for surgery and renal replacement therapy prior to the onset of BSI within 30 days.

In the multivariate logistic regression model (Table 4), the risk factors for 7-day mortality included increasing APACHE II scores (OR 1.2, 95% CI 1.1–1.3), and the use of immunosuppressive agents prior to the onset of enterococcal BSIs (OR 4.6, 95% CI 1.1–19.2); the risk factors for 30-day mortality included impaired renal function (OR 3.3, 95% CI 1.1–9.8), high CCI (OR 1.3, 95% CI 1.1–1.6) and APACHE II scores (OR 1.3, 95% CI 1.2–1.4), and prior exposure to immunosuppressive agents (OR 7.3, 95% CI 1.8–29.0). Appropriate empirical antimicrobial therapy was a protective factor for both 7-day (OR 0.2, 95% CI 0.1–0.7) and 30-day mortality (OR 0.2, 95% CI 0.1–0.4).