In the present study, we carried out a retrospective cross-sectional study from 1 January, 2017 to 30 June, 2020 in Department of PICU, SICU, CICU and GICU to analyze the positive blood cultures isolated from patients with BSIs. The current study demonstrated that the microbial distribution and antibiotic susceptibility exhibited a high divergence among BSIs in different ICUs. Therefore, different antibiotic therapies for various wards and distinct age groups were suggested to prevent highly antibiotic-resistant infections, especially in RICU and GICU.
BSIs comprise a wide variety of pathogens and clinical syndromes with quite diverse risk factors, therapeutic implications and outcomes. The infections occur when one or more pathogens invade the bloodstream, usually causing a systemic inflammatory response syndrome (SIRS) [9]. BSIs were defined as the isolation of pathogenic organisms from at least one blood culture sample. The detection of the causing pathogen by using molecular techniques has been proven suboptimal and blood culture remains the gold standard and first line tool in the pathogen diagnostics of BSIs and sepsis [10]. Microbiological cultures of blood specimens provided clinically relevant information concerning the identity and analysis of microorganisms with their susceptibility to antibiotics. We found that blood specimens of the RICU had the highest positive frequency (9.48%), similar to the finding in an India tertiary care institute where SIRS-related sepsis and BSI were 11.5% in the RICU [11]. Previous studies have observed a percentage of positive blood culture from 7 to 9.89% in children [12, 13], and the presence of BSIs was also relatively high (8.36%) in our PICU, probably due to the immature state of children’s immune system predisposing them to infections.
In this study, the distribution of microorganisms isolated from blood specimens showed that the total proportions of Gram-positive bacteria in the PICU, SICU, CICU and GICU were all much higher than Gram-negative bacterial strains. Among these positive blood cultures, several frequently isolated pathogens were S. hominis, S. epidermidis and S. capltis which belong to coagulase-negative staphylococci (CoNS). In recent years, CoNS have become true pathogens, rather than simply culture contaminants, causing BSIs and cardiovascular infections among other conditions [14]. Another research also reported a similar finding that CoNS were the common causative agents of BSI in European populations [15]. Moreover, Enterococcus spp. (such as E. faecalis and E. faecium) was one the prevalent organisms in the PICU, SICU and GICU, and S. aureus was the second most frequent bacterium in CICU, which might indicate that skin, soft tissue, bone and joint sources of infection caused BSI by Gram-positive cocci such as S aureus, enterococci, and streptococci. In our PICU, the major bacterium was Gram-negative Acinetobacter baumannii, followed by S. epidermidis and E. faecalis. However, Singhi S et al. from India [16] and Maham S et al. from Iran [17] observed Gram-negative bacteria as the predominant isolates of pediatric BSIs, common being K. pneumoniae (20.1% and 8.8%) and Acinetobacter spp. (8.6% and 7.9%). The difference between our research and theirs may be due to the distinct social, economic and environmental factors in these regions. K. pneumoniae was the most frequent pathogen in three of the five ICUs (SICU, CICU and RICU), consistent with a recent review showed that Klebsiella spp., the second (behind E. coli) overall cause of Gram-negative BSI, have been and remain one of key pathogens from high income countries [1]. In the GICU, the dominant microorganism was E. coli which was also reported as the most prevalent pathogen by a previous research based on the Swiss ANRESIS, revealing the incidence of BSIs increased throughout the study period 2008–2014, especially among geriatric patients [3]. According to our study, there was a high divergence between pediatric and geriatric patients. A 3-year multicenter retrospective study showed that individuals aged 0–5 years and ≥ 40 years old were the main demographics at risk of infection by E. coli, K. pneumoniae, A. baumannii, while individuals aged 0–5 years were the major demographic at risk of infection by S. aureus, E. faecalis, E. faecium, etc [18]. RICU was the only ICU where Gram-negative bacteria remained the key microorganisms involved in BSIs because Enterobacteriaceae spp. (such as K. pneumoniae) might be the predominant microorganisms in respiratory tract infection patients [8, 19].
In the hospital setting, intensive and prolonged use of antimicrobial drugs introduces the emergence and spread of highly antibiotic-resistant infections [20]. Currently, antimicrobial resistance is one of the most serious global public health threats which call for action from all of society. In order to achieve appropriate therapeutics, updated epidemiology of antimicrobial sensitivity is required to support therapeutic guidelines. In the present study, we observed that S. hominis of BSIs remained highly susceptible (> 70%) to gentamicin, linezolid, daptomycin, teicoplanin, vancomycin, tigecycline and rifampicin in all the ICUs. Its antibiotic sensitivity to levofloxacin was moderate in the PICU and CICU, but mild (< 30%) in the SICU, RICU and GICU. Moreover, methicillin-resistant coagulase-negative Staphylococcus (MRCNS) was one of the major resistance patterns of positive isolates from the ICUs in our hospital, and a four-year retrospective survey in a Japanese tertiary hospital revealed that MRCNS bacteremia (diagnosed as two or more positive blood cultures on the same day with clinical signs of infection) was associated with a low mortality rate, and suggested that glycopeptides, especially teicoplanin, must be used appropriately to prevent antibiotic resistance in MRCNS [14]. It is vital to treat staphylococci infections as the increasing proportion of CoNS isolates presented as methicillin-resistant. S. aureus was highly susceptible to linezolid, daptomycin, teicoplanin, vancomycin, tigecycline and rifampicin in all the ICUs, and the susceptibility to oxacillin, gentamicin, levofloxacin and moxifloxacin was high in PICU, high or moderate in CICU and SICU, while mild in the RICU and GICU. A review of 15 studies showed that between 13 and 74% of worldwide S. aureus infections are methicillin-resistant Staphylococcus aureus (MRSA) [21], and the mortality rate from MRSA BSI was 25.3% [22], which remain a major healthcare issue. In general, for both S. hominis and S. aureus isolated from BSIs, RICU and GICU exhibited more serious antibiotic resistance than other ICUs (such as PICU and CICU) in our hospital. E. faecium exhibited highly susceptible to linezolid and tigecycline in all the ICUs, and it was highly susceptible to teicoplanin and vancomycin in PICU, SICU and GICU (except RICU and CICU). A meta-analyses revealed that the prevalence of vancomycin-resistant Enterococcus (VRE) infections in Iran was 9.4 % among culture-positive cases for Enterococcus spp, and the prevalence of VRE in developed countries, such as Germany, the United Kingdom (UK), and Italy was 11.2 %, 8.5–12.5 %, and 9 % respectively [23]. Olivier CN et al observed that of the 768 patients colonized with VRE, 4.0% usually developed VRE bloodstream infections due to a related strain [24]; therefore, continuously monitoring trends in the microbiology of BSI pathogens is very important. As a predominant Gram-negative bacterium in blood cultures, K. pneumoniae was highly susceptible to doxycycline, minocycline, tigecycline in all the ICUs except RICU, and its antibiotic sensitivity to imipenem, meropenem, amikacin, ciprofloxacin and levofloxacin in the GICU was high or moderate in PICU, CICU and GICU, but mild in the SICU and RICU. K. pneumoniae is common causes of health care- and ICU-acquired infections, and one of key pathogens from bacterial BSIs [1]. Increasingly used carbapenem has contributed significantly to the emergence and rapid dissemination of carbapenem-resistant K. pneumoniae (CRKP) strains [25, 26]. The resistance patterns such as carbapenem-resistant Enterobacteriaceae (CRE) (including CRKP, carbapenem-resistant Pseudomonas aeruginosa [CRPA], etc.) and carbapenem-resistant A. baumannii (CRAB) have been increasing in recent years. In the ICUs of our hospital, A. baumannii only exhibited highly susceptible to tigecycline, and mildly sensitive to imipenem and meropenem. And its susceptibility to ceftazidime, cefepime, tobramycin, levofloxacin, doxycycline and minocycline was moderate in PICU, but mild in the SICU and RICU. Liu Y et al conducted a prospective multi-center study in China and suggested that carbapenem resistance has a significant impact on mortality for patients with A. baumannii complex BSI [27]. E. coli was highly susceptible to the tested antibiotics in the CICU, whereas it exhibited moderate or relatively low drug-susceptibility to the antibiotics (except doxycycline, minocycline and tigecycline) in the PICU, SICU and GICU. In our study, for K. pneumoniae, A. baumannii and E. coli isolated from BSIs, RICU, SICU and GICU exhibited more serious antibiotic resistance than other ICUs. The phenomenon may result from inadequate empirical use of antimicrobials for patients with respiratory tract infections or to avoid suspected infection surgical operations. And age probably a main contributor to the multidrug-resistant bacteria emerged among the geriatric patients undergoing prolonged treatments with broad-spectrum antibiotics.
However, our research has certain limitations, partly because it was only focused on BSIs from one tertiary hospital in Beijing, which might have led to enrollment bias considering the geographic location.