Epidemiology and microbiology of Gram-positive bloodstream infections in a tertiary-care hospital in Beijing, China: a 6-year retrospective study

BSIs are serious diseases associated with high morbidity and mortality, which are diffcult to treat and ofen result in a heavy social and economic burden [1]. In China, BSIs account for one-third of healthcare-associated infection, followed by lower respiratory tract and urinary tract infections [2]. Acoording to a resent USA_based prevalence surey, Gram-positive pathogens were the most frequently isolated pathogens among BSIs [3]. Acoording to CHINET, the most commonly gram-positive in 2010 were Staphylococci, Enterococcus spp. and Streptococcus spp. [4, 5]. In addition, some studies have reported that the crude incidence of BSIs varies from country to country [6–8].

Over recent years, due to the widespread use of antibiotics, immunosuppressants and anti-tumour drugs, and the increase of invasive medical examinations and treatments, the epidemiology and antimicrobial resistance have been changing. Multidrug resistant patterns in Gram-positive bacteria have resulted in difficult-to-treat or even untreatable cases, which in tum caused the increase in mortality. E.g. recent ECDC data from 2013 indicated a global increase in methicillin-resistant staphylococcus aureus (MRSA) (> 50%) isolated from blood, and a higher rate in vancomycin- resistant Gram-positive coccus in Europe [9–11]. Morever, Enterococcus spp. has shown increasing prevalence of acquired resistance to penicillins, aminoglycosides and vancomycin, which was observed in many countries [12, 13]. A report from Europe has shown that there were more than 1.2 million episodes of BSIs with 157,000 deaths per year, while between 57,500 and 677,000 episodes of BSIs were reported in North America causing some 79,000 to 94,000 deaths [14].

Although there are number of study on BSIs, few data reports have focus on Gram-positive bacteria- BSIs and the epidemiology and antimicrobial resistance of various BSIs in different periods and regions, thus making it very difficult to timely choose antibiotic treatment based on the empirical evidence. Therefore, the purpose of this study was to provide more data on the incidence, microbiological features, mortality and drug resistance data at our hospital.

We performed a retrospective cohort study in patients with Gram-positive bacterial bloodstream infections between January 1, 2011, and June 31, 2017 at the Chinese People’s Liberation Army General Hospital (PLAGH), a 2200-bed tertiary-level healthcare facility in Beijing, China.

Eligible patients included all patients with at least one positive blood culture for Gram-positive bacteria. In patients with persistent BSIs caused by the same organism, only the first episode was included within the previous 30 days. If 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) [15]. This platform utilizes data from electronic medical record systems, such as sex, hospital ward, comorbidity, and microbiology results, with the application of clinically validated algorithms to identify and classify all of the patients’ infections. The infection management and disease control department of PLAGH developed RT-NISS. In addition, since Gram-positive bacilli are not routinely identified at our hospital, patients with those types of bacteria were excluded them from the study.

This study examined the incidence and characteristics of Gram-positive bloodstream infections in one of the largest tertiary-care hospitals in China. So far many studies have reported epidemiology, species distribution and antibiotic resistance of Staphylococci, Enterococcus spp. Streptococcus spp. Gram-positive bacilli and others [18–20], neverthless, only few studies have focused on Gram-positive bloodstream infections [21].

In our 6-year study, the incidence of Gram-positive BSIs switched order from 4.6 to 7.3 episodes per 10,00 admissions over 6 years. Acoording to our knowledge, thus far no such data, i.e. incidence rates of Gram-positive BSIs based on large retrospective studies have been reported. In the present study, a downward trend was observed in overall incidence in the ICU per year, while there was no obvious change on general ward. This might be explained with the increased importance of prevention and control infection among medical staff of ICU that was obvserved over recent years. Nevertheless, two recent studies haved reported an increase in the incidence of Gram-positive BSIs in general ward and ICUs [22, 23].

BSIs are commonly associated with comorbidities, such as malignancies, diabetes mellitus and infections [24, 6]. In the present study, we found that malignancy was the most common comorbidity, and the major predisposing factor for BSIs was indwelling central intravenous catheters; this data was consistent with previous results [25, 26]. Several studies have reported that the second most common factors is abdominal and lower respiratory tract infections [27, 18]; while we found that chemoradiotherapy was the second most common factor for BSIs. The observed differences might be due to the fact that the malignancy was the most common comorbidity with extensive use of intravascular catheters for chemotherapy and the high rate of radiotherapy, which more commonly lead to BSIs.

In our study, 69% of infections were healthcare-associated while 31% were community-associated (69% VS 31%). We hypothesized that this occurred due to the following reasons: first, the study population was mainly focused on healthcare-associated infection, and blood collection and culturing was a routine examination for hospitalized patients with fever. Another reason was that the common predisposing factors of Gram-positive BSIs such as central intravenous catheters, immunosuppression, and chemoradiotherapy were mainly found with hospitalized patients in our study. Beyond that, we have found that a rate of Streptococcus pneumoniae infection in China is significantly lower compared to other developed countries [28]. Pneumococcal vaccine is routinely used to treat streptococcus pneumonia disease in developed countries, which might affect the morbidity and mortality [29]. Nevertheless, China is still facing great challenges, such as uncomplete network for monitoring infection with streptococcus pneumoniae and lack of relevant immune policy for standardized use of pneumococcal vaccine. Moreover, besides PPV23 there is no available vaccine in China.

In our study, Staphylococci was 100% sensitive to vancomycin and linezolid except for Staphylococcus epidermidis, for which the vancomycin resistance rate was 0.13%. These results were consistent with the studies by Fayez et al. [30]. However, Mamishi and colleagues have reported an obviously higher prevalence of resistance to penicillin by Streptococcus pneumonia, i.e. 42.86% in Asian countries [31]. The reason might be the wide use of the variety of interventional procedures, immunosuppressive agents and vancomycin, so it is necessary to strengthen monitoring drug resistance and rational use of antibiotics in clinical. All of the cases of Staphylococci showed more than 90% resistance to penicillin except for MRSA. However, Vasudeva has reported that all Staphylococci showed are 100% resistant to penicillin [32, 33]. This may be related to the different practical uses of β-lactam antibiotics in various areas, resulting in different drug resistance to bacteria. Mover, the resistance rates of Staphylococci to gentamicin and tetracycline were less than 50%, Staphylococcus epidermis which was consistent with the previous studies [21, 34]. Therefore, both gentamicin and tetracycline might be good treatment choice against Staphylococci used to decrease the overwhelmingly dependent on vancomycin and linezolid.

In our study, all of the vancomycin-resistant isolates were E. faecium (4.1%), which was lower compared to number of other studies from US and Europe [35, 36]. Both E. faecalis and E. faecium have shown resistance to linezolid (3.8% and 3.1%), which was similar to the results from two studies from China [18, 21], nonetheless, resistance to linezolid was rarely reported in foreign studies [37]. This may be explained with the species distribution and antimicrobial resistance that varies geographically. In addition, there were 219 (44%, 95%CI 38–50%) patients who were treated with effective antibiotics before obtaining the report of antibiotic susceptibility. Test reports have shown that patients with E. faecalis BSIs are more likely to receive effective treatment by the empirical use of antibiotics (61% vs 35%, p = 0.013). This may be explained by the low resistance rate of E. faecalis to many antimicrobial agents, such as penicillin (9.1%), ampicillin (11.4%), gentamicin (31.4%), and ciprofloxacin (35.6%).

In our study, there was no vancomycin and linezolid resistance to streptococcus pneumoniae and viridians streptococci, which was consistent with the studies done by Fayez and Marshall [30, 33]. Viridians streptococci was 100% sensitive to penicillin, but two other studies have reported that penicillin resistance rates have increased to more than 50% [38, 39]. The penicillin resistance rate of Streptococcus pneumoniae was 30%, similar to many European countries (20% to 50%), although much higher rates were reported in other Asian countries [40, 41], while there were only a few countries with lower rates (less than 10%) [9, 32, 42]. Therefore, the penicillin aslo resulted as a treatment choice for Streptococcus spp.

In our study, the crude mortality of Gram-positive BSIs and the mortality of Enterococcus spp. and Streptococcus spp. have shown a significant downward trend from 2011 to 2017. One possible reason might be that the number, correct timing and accuracy of blood cultures were all greater in a tertiary-care hospital thus medical workers could more correctly choose antibiotics in a timely manner. Further, there is a greater choice of antibiotics in non-tertiary hospitals. Another reason might be that tertiary-care hospitals have more complete strategy for strict control of infection that can reduce the mortality factors in BSIs. The mortality in the ICU has shown a decreased trend, while the general ward revealed contrary results. This could be explained by certain proportion of surgical and critically ill patients at our hospital, although many previous studies have shown that these patients have higher mortality rates than patients at the general ward [22, 23]. Nonetheless, the diagnosis and treatment technologies of ICU such as ventilator and ECMO have been rapidly developing rapidly over recent 5 years, and a variety of positive treatment measures have shown effective to improve cure rate and reduce mortality. Some other reasons that highlighted the importance of infection control measures among the medical staff of ICU are strict aseptic operations, good hand hygiene and similar. On the contrary, the use of indwelling central intravenous catheter seem to be increasing because of more chemotherapy and venous nutrition employed at general ward, while the consciousness of medical staff related to BSIs remained weak and the maintenance measures related to central intravenous catheter remained not enough strict. Aslo and the patients at general ward later received the empirical treatment thus further increasing the mortality.

There are several limitations in the present study that should be considered. First, the collection of clinical data depended on medical records rather than interviews and the comprehensive assessment of clinical symptoms. Second, there was an inevitable bias this was a single-centre study, and some of the results might have been affected by the small sample size. Finally, many drug susceptibility results could not be evaluated because of a lack of unified standards aslo and not all isolates underwent the same antimicrobial agent sensitivity tests, so many isolates lacked resistance comparisons with other isolates in the present study.

Gram-positive BSIs are the major cause of high morbidity and mortality, especially in patients with chronic disease and predisposing factors. However, in this study we found a decrease in morbidity and mortality, while the mortality at the general ward revealed the opposite trend. Although the resistance rates to vancomycin and linezolid among the Gram-positive BSIs increased, these antibiotics are still considered the best treatment options for patients with Gram-positive BSIs.