Staphylococcus aureus bloodstream infection in a Chinese tertiary-care hospital: A single-center retrospective study.

To the Editor: Despite major advances in medical care, the incidence and mortality of bloodstream infection (BSI) remain high, which is still a global public health challenge. BSI can be caused by various microorganisms, and the most common organisms are Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus (S. aureus), according to the China Antimicrobial Surveillance Network (CHINET).[1]S. aureus is the third most common cause of BSI, which is associated with short-term mortality rates of 15–30%, long-term excess mortality, and increased healthcare costs. At present, there are many studies on Gram-negative bacteremia but relatively few on S. aureus bloodstream infection (SA-BSI), especially in China. With the occurrence of new treatments and clinical conditions, such as aging and extensive antibiotic resistance, it is necessary to reanalyze the clinical characteristics and prognosis of SA-BSI. This single-center retrospective cohort study was conducted in the Second Affiliated Hospital, Zhejiang University School of Medicine. The Ethics Committee of our hospital granted ethics approval (No. 2019-194) for the present study. The requirement for signed informed consent was exempted because of the retrospective nature of the study. Furthermore, a statement of permission from patients for submission was not needed, as no personal information was included. During the six-year study period (2013–2018), a total of 1174 blood culture specimens positive for S. aureus were initially included. Four patients aged <18 years, 54 patients with nonpathogenic bacteria, 45 patients with incomplete or missing data, and nine patients lost to follow-up were excluded. Finally, 349 patients were included. The patients were followed for at least 28 days after the onset of BSI. According to 28-day mortality, the patients were divided into nonsurvival (61 cases) and survival groups (288 cases) [Figure 1A].Figure 1: (A) Flowchart of study participant enrollment with blood culture specimens positive for Staphylococcus aureus. (B) Age and sex distributions of patients with SA-BSI. (C) Distribution proportions of MRSA and MSSA from 2013 to 2018. (D) Forest plot of the results of the univariate and multivariate logistic regression analyses for prognostic factors for death in patients with SA-BSI. APACHE: Acute Physiology and Chronic Health Evaluation; COPD: Chronic obstructive pulmonary disorder; CVC: Central venous catheter; ICU: Intensive care unit; MRSA: Methicillin-resistant Staphylococcus aureus; MSSA: Methicillin-sensitive Staphylococcus aureus; SA-BSI: Staphylococcus aureus bloodstream infections; SOFA: Sequential Organ Failure Assessment.Using a self-created Excel sheet, the clinical data of cases were collected through the hospital identification of blood culture-positive specimens for S. aureus provided by the microbiology laboratory. We recorded demographic and microbiological data, sensitivity to antibiotics, and clinical treatment and evaluation data (the Sequential Organ Failure Assessment [SOFA] score, the Acute Physiology and Chronic Health Evaluation [APACHE] II score in the first 24 h following the onset of BSI) by reviewing electronic medical records. To ensure data quality, a homogeneous data collection form was carefully prepared before data collection. Additionally, two days of training were provided to data collectors and supervisors. Furthermore, the supervisor and principal investigators supervised the data collectors throughout the entire data collection period. After data collection was completed, the supervisor organized and carefully cleaned the data and then entered the data into Statistical Package for Social Sciences (SPSS, 26.0, IBM Corp., Armonk, NY, USA) for statistical analysis. Variables with P <0.05 in the univariate analysis were entered into the multivariable model. Continuous variables were treated as dichotomous variables based on Youden index. Multivariate analysis was performed with logistic regression to identify independent prognostic factors for death in patients with SA-BSI. A two-tailed P <0.05 was considered statistically significant. The demographics showed that the median age was 59.0 (45.5–68.0) years, and 69.6% (243/349) were male [Supplementary Table 1, https://links.lww.com/CM9/B557]. The age distribution was left-skewed, with a peak incidence in the group of 60–69 years. In addition, the proportion of men was significantly higher than that of women in all age groups except for those >90 years old [Figure 1B]. Patients in the nonsurvivor group were significantly older than survivor group (median, 65.0 vs. 58.0 years, P = 0.005). In terms of comorbidities, significantly higher percentages of chronic obstructive pulmonary disease (COPD) and severe asthma were observed in the nonsurvivor group than in the survivor group (6.6% [4/61] vs. 1.0% [3/288], P = 0.005). In comparison with survivors, nonsurvivors had a more severe condition, evidenced by a higher APACHE II score (median, 24 vs. 11, P <0.001), a higher SOFA score (median, 12 vs. 3, P <0.001), and had a higher rate of intensive care unit (ICU) admission (85.2% [52/61] vs. 27.4% [79/288], P <0.001), indwelling central venous catheter placement (73.8% [45/61] vs. 42.4% [122/288], P <0.001), and invasive mechanical ventilation (82.0% [50/61] vs. 34.4% [99/288], P <0.001). Compared with those in survivors, the proportions of polymicrobial SA-BSI (26.2% [16/61] vs. 13.2% [38/288], P = 0.011), methicillin-resistant S. aureus (MRSA) (82.0% [50/61] vs. 57.3% [165/288], P <0.001), and septic shock (50.8% [31/61] vs. 1.4% [4/288], P <0.001) in nonsurvivors were higher. In comparison with survivors, nonsurvivors had a lower hematocrit (median [%], 26.8 vs. 29.1, P = 0.009), a lower platelet count (median [109/L], 85 vs. 187, P <0.001), a lower albumin level (mean [g/L], 27.73 vs. 29.95, P =0.005), and worse liver and kidney function. In addition, the absolute neutrophil count (ANC) and procalcitonin (PCT) level were significantly higher in nonsurvivors than in survivors [Supplementary Table 2, https://links.lww.com/CM9/B557]. In comparison with those in survivors, the ratios of resistance of S. aureus to ciprofloxacin, levofloxacin, and moxifloxacin were significantly higher in nonsurvivors [Supplementary Table 3, https://links.lww.com/CM9/B557]. Of note, MRSA occurred significantly more frequently in nonsurvivors than in survivors (82% [50/61] vs. 57.3% [165/288], P <0.001). The proportion of MRSA had a significant downwards trend from 70.8% (46/65) in 2014 to 43.6% (24/55) in 2018 [Figure 1C]. The main source of SA-BSI was pneumonia (26.6%, 93/349), followed by skin/soft tissue infection (24.4%, 85/349). Compared with survivors, nonsurvivors had higher rates of pneumonia (37.7% [23/61] vs. 24.3% [70/288], P =0.032) and intra-abdominal infection (27.9% [17/61] vs. 8.7% [25/288], P <0.001) [Supplementary Table 4, https://links.lww.com/CM9/B557]. In terms of infection control, there was no significant difference in the rates of drainage of the infection source and removal of contaminated sutures between the two groups. We also did not observe any differences in mortality between the survivors and nonsurvivors based on antibiotic exposure (P >0.05). For targeted treatment, 189 (54.2%) patients received glycopeptides (vancomycin or teicoplanin), 25 (7.2%) patients received piperacillin/tazobactam, 58 (16.6%) patients received linezolid, 26 (7.4%) patients received tigecycline, and 43 (12.3%) patients received fluoroquinolone (levofloxacin or moxifloxacin), but there was no statistical significance between the two groups. In addition, a total of 8.3% (29/349) of patients did not receive appropriate therapy within 24 h after the release of antibiotic susceptibility results, but there was no difference between the two groups (6.6% [4/61] vs. 8.7% [25/288], P =0.585) [Supplementary Table 4, https://links.lww.com/CM9/B557]. The multivariate logistic regression model showed that the independent prognostic factors for 28-day mortality were age >67 years (adjusted odds ratio [aOR], 4.46; 95% confidence interval [CI], 1.18–16.88), an APACHE II score >17 (aOR, 42.47; 95% CI, 8.11–222.48), a SOFA score >7 (aOR, 8.01; 95% CI, 2.06–31.12), septic shock (aOR, 9.86; 95% CI, 1.18–82.37), and albumin <30 g/L (aOR, 5.14; 95% CI, 1.34–19.71) [Figure 1D]. There is still some controversy about the relationship between polymicrobial BSI and mortality in ICU patients. A study by Park et al[2] showed that polymicrobial SA-BSI was an independent prognostic factor for bacteremia-related mortality, which is not consistent with our current study. In their study, patients with polymicrobial SA-BSI were significantly less likely to receive appropriate empirical antibiotics than those with monomicrobial SA-BSI; 25% were infected with S. aureus plus a Gram-positive pathogen; and evidence did not shown that coinfection with Gram-positive pathogens resulted in death faster than coinfection with Gram-negative organisms. In our study, appropriate antibiotic therapy did not differ between the two groups, and the proportion of Gram-positive coinfections (36.1% [22/61]) with S. aureus was significantly higher than that in the study by Park et al[2] (25%). Therefore, we speculate that fatal polymicrobial SA-BSI is associated with a more severe condition and is not a direct independent prognostic factor of death for patients with SA-BSI. The incidence of SA-BSI has generally been reported to be higher in males than in females, while some studies have reported increased mortality in females.[3] We found that most of the proportions of infections in males in the different age groups were generally higher than those in females [Figure 1B], and the mortality rates of SA-BSI in men and women were 19.3% [47/243] and 13.2% [14/106], respectively. We did not detect any sex difference in outcomes. We found that the age distribution was left-skewed, with a peak incidence in the 60–69 years group [Figure 1B], and age >67 years was an independent prognostic factor for death in patients with SA-BSI. This might be related to more comorbidities in older patients. As described in many studies,[3] age was the strongest independent predictor of mortality, and the mortality rate increased from 6% in young individuals (<15 years old) to 57% in adults >85 years of age according to Lamagni et al.[4] Therefore, clinicians should pay more attention to the age of patients with SA-BSI than to their sex. In our current study, the proportion of MRSA had a significant downwards trend from 70.8% (46/65) in 2014 to 43.6% (24/55) in 2018, which is in line with the MRSA trend reported by CHINET,[3] probably as a result of a greater understanding of SA-BSI management. Although MRSA was associated with mortality, it was not an independent prognostic factor for death in patients with SA-BSI. This might be related to a decrease in the pathogenicity of MRSA in recent years, which is indirectly refected by the decrease in the detection rate of MRSA in our hospital in recent years. In addition, we found that septic shock was an independent prognostic factor for death in patients with SA-BSI. In conclusion, SA-BSI was characterized by a peak incidence in 60–69 years old, and pneumonia and skin/soft tissue infection as the main infection sources. There were several independent prognostic factors for 28-day mortality of SA-BSI patients, including age >67 years, an APACHE II score >17, a SOFA score >7, septic shock, and albumin <30 g/L. By contrast, MRSA and polymicrobial BSI were associated with 28-day mortality, but not independent prognostic factors. To properly manage SA-BSI, clinicians should be aware of patients with one or more of the abovementioned independent prognostic factors. Funding This work was supported in part by grants from the National Natural Science Foundation of China (No. 81901941), Natural Science Foundation of Zhejiang Province (No. LY19H150007; No. LY20H150008), Medical and Health Research Program of Zhejiang Province (No. 2019RC038; No. 2018KY427; No. 2022KY1396, No. 2022KY1398). Conflicts of interest None.