Trends of Bloodstream Infections in a University Hospital During 12 Years

Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide, in both developed and developing countries (Tian et al. 2019). They are among the top seven causes of death in Europe and North America, with more than two million episodes each year and a case fatality rate of 13–20%, resulting in 250,000 deaths annually. Approximately 30% of patients with BSI receive ineffective or delayed antimicrobial therapy, which in turn causes increased antimicrobial resistance and mortality (Pfaller et al. 2020). For this reason, in 2015, the World Health Organization published the Antimicrobial Resistance Global Action Plan to promote awareness and understanding of antimicrobial drug resistance (WHO 2015). In addition, studies conducted in the last decade have associated an increase in the incidence of BSI with a sharp rise in at-risk population numbers (elderly patients, those with chronic diseases or immunosuppression, etc.). These developments are central to the global spread of multiresistant bacteria. Therefore, monitoring changes in the rate of BSI caused by pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase (ESBL) or carbapenemase-producing Enterobacteriaceae is key to improving their management and prevention, as well as ensuring the delivery of appropriate health-care (Diekema et al. 2019; Sader et al. 2019; Martínez Pérez-Crespo et al. 2021).

This study aims to investigate the prevalence of pathogens responsible for BSI, and their antimicrobial susceptibility profiles, in patients at our tertiary care university hospital for 12 years. Understanding the disease burden of BSIs can provide a valuable indicator for healthcare providers.

In our hospital, from 2008 to 2019, a total of 136,030 blood cultures were processed for 34,782 patients from wards and ICUs. Of these, 11,542 isolates identified in 10,584 blood culture bottles from 7,096 patients were included in this study, while 11,443 isolates identified in 10,232 blood culture bottles from 4,460 patients were deemed contaminated according to CDC criteria and therefore were excluded from the study. Our contamination rate (10,232/136,030) was calculated to be 7.5%.

In our study, 8,891 BSI episodes occurred among 7,096 (4,016 – 56.6% male and 3,080 – 43.3% female) patients. Proportions of species are shown in Table I. 80.4% of samples were collected from wards, and 19.6% from ICUs. The overall rate of polymicrobial episodes was 19.4%, with significantly higher numbers in ICUs (27.7%) compared to hospital wards (17.3%) (chisquare; p < 0.001).

In the analysis of monomicrobial growths, E. coli was the most commonly seen Gram-negative (11.6%) and CoNS the most common Gram-positive (10.1%) agent. The most commonly found fungi were Candida parapsilosis (2.7%) and Candida albicans (2.5%). In polymicrobial growth analysis, although E. coli was the most common accompanying agent in the wards and overall, A. baumannii was the most frequent in ICU patients. When we evaluated polymicrobial and monomicrobial growth together, CoNS (12%) emerged as the most common pathogen, followed by E. coli (11.8%), K. pneumoniae (8.9%), S. aureus (8.6%), A. baumannii (7.6%), and P. aeruginosa (5%).

Fig. 1 and 2 show the frequency of microorganisms within all positive blood cultures. There was a significant decrease in the overall frequency of polymicrobial and CoNS isolates over the study period; the frequency of K. pneumoniae isolates increased significantly on the wards and in ICUs, whereas the frequency of S. aureus isolates decreased significantly in ICUs (Fig. 1).

Fig. 2 shows the frequency of resistant strains within all positive blood cultures. Vancomycin-resistant enterococcus (VRE) rates in both wards and ICUs have remained unchanged over the 12 years, while the rate of MRSA in ICUs has decreased significantly. Overall, ESBL-positive E. coli and K. pneumoniae, carbapenem-resistant E. coli and K. pneumoniae, and colistin-resistant K. pneumoniae and A. baumannii have all increased significantly over the years.

Fig. 1

Fig. 2

Tables II and III show the resistance rates of the most common bacteria at different points during the 12 years. In E. coli, we found that resistance against cefotaxime, cefepime, and gentamicin was significantly more common in the isolates from ICU patients than in the wards (Table II). ESBL-positive E. coli bacteremia rate was 37.1%, and there was no statistically significant difference between ICU and non-ICU settings. In patients with K. pneumoniae infection, resistance rates for all antibiotics were found to be significantly higher in ICU patients. ESBL-positive K. pneumoniae bacteremia rate was 48.7% and carbapenem-resistant K. pneumoniae bacteremia rate was 37.1%. The resistance rate was significantly higher in the ICU setting. A. baumannii, resistance to cefotaxime, cefepime, imipenem, meropenem, piperacillin-tazobactam, gentamicin, and ciprofloxacin was significantly higher in ICU patients. Regarding P. aeruginosa, resistance to cefepime, imipenem, meropenem, piperacillintazobactam, gentamicin, and ciprofloxacin was also found to be significantly higher in ICU patients than in the wards (Table II).

When we investigated Gram-positive bacteremia, daptomycin, vancomycin, and linezolid-resistant S. aureus were not detected. However, oxacillin-resistant S. aureus (an indicator of MRSA) was significantly higher in ICU patients. While daptomycin and vancomycin resistance was not detected in CoNS, oxacillin resistance (indicating MRCoNS) was also found to be significantly higher in ICU patients. In the E. faecalis and E. faecium isolates, penicillin resistance was found to be significantly higher in non-ICU patients (Table III).

The incidence of BSI episodes per year and over 12 years was calculated as a ratio of 10,000 hospital bed days and 1,000 hospital admissions. The incidence of BSI in our hospital over the 12 years was 20.8/10,000 bed days, and 10.2/1,000 admissions. An inverse correlation was demonstrated for MRSA isolates in 10,000 bed days (r = –0.978, p = 0.022) and 1,000 admissions (r = –0.977, p = 0.023) when calculating annual incidence rates. In other resistant strains, no significant correlation (direct or inverse) was found per 10,000 hospital/ unit bed days or 1,000 hospital/unit admissions.

Our study is important for highlighting changes and trends in the frequency of bacteremia isolates and their antibiotic resistance detected in our hospital over a long period. CLSI guidelines advocate a target of < 3% contamination rate in blood cultures (CLSI 2007). However, in studies from different geographical regions and countries with diverse socioeconomic levels, a higher rate of 3.8–10.4% has been reported, which is similar to our results of 7.5% (Chukwuemeka and Samuel 2014; Abu-Saleh et al. 2018). A German study reported a 2.8% contamination rate in blood cultures (Schöneweck et al. 2021).

Our hospital is a tertiary care hospital with low staffing levels, a heavy workload, and an increasing frequency of invasive procedures. All these contribute to the cross-infection with microorganisms from patient to patient. It may account for our high contamination rate (7.5%). However, we found a significant decrease in the overall frequency of CoNS isolates in samples, related to the contamination rate.

S. aureus is the leading cause of Gram-positive bacteremia worldwide, while E. coli is the most significant cause of Gram-negative bacteremia (Hattori et al. 2018; Tian et al. 2019; Pfaller et al. 2020). In a study conducted in Iran, CoNS was found to be the most common Gram-positive pathogen while the most common Gram-negative bacteria was P. aeruginosa (Keihanian et al. 2018). In two other studies conducted in our country, the most common Gram-positive pathogen were E. faecalis (Satılmış and Aşgın 2019) and S. epidermidis (Bıçak et al. 2020), with E. coli the most common among Gram-negative bacteria. In our study, CoNS was found frequently in Gram-positive bacteria, a result of our high contamination rate. Meanwhile, similar to the literature, E. coli was the most common Gram-negative bacterium.

The prevalence of polymicrobial infection in BSI episodes is reported to vary between 8–32% (Yo et al. 2019). Similarly, in our study, this rate was 19.4%. According to the international EUROBACT study, which examined BSIs in 162 ICUs; monomicrobial growth was reported in 88% of the patients (58.3% Gram-negative, 32.8% Gram-positive, 7.8% fungal, 1.2% anaerobic), while polymicrobial growth was reported in 12% (Tabah et al. 2012). Similar to these results and those of other studies, we found Gramnegative bacteria to be the most common etiological agents for BSI in the ICUs, and Gram-positive bacteria emerged as the second most common cause (Tabah et al. 2012; Chaturvedi et al. 2021; Kallel et al. 2021).

Changing trends in the prevalence of pathogens caused by BSI have also been recorded. The SENTRY study group and two other studies have described an increase in the prevalence of K. pneumoniae in BSIs over time (Li et al. 2020; Pfaller et al. 2020; Tsuzuki et al. 2021). A study from Greece, our neighboring country, noted using data from WHONET that although the prevalence of K. pneumoniae in hospital wards has decreased in past years, it has increased in ICUs (Polemis et al. 2020). In contrast, in our study, we saw a significant increase in the prevalence of K. pneumoniae – overall in hospital wards and ICUs. One SENTRY study (Pfaller et al. 2020) found the prevalence of MRSA to be decreasing over time, while another SENTRY study (Diekema et al. 2019) noted an increase in ESBL-positive E. coli and K. pneumoniae, and carbapenem-resistant Enterobacteriaceae. Studies conducted in China reported the increasing incidence of carbapenem-resistant K. pneumoniae (Tian et al. 2019; Mineau et al. 2018) and MRSA in hospital wards (Tian et al. 2019), but a decrease in MRSA and ESBL-positive K. pneumoniae in ICUs (Tian et al. 2019). Meanwhile, ESBL-positive E. coli has increased in ICUs in Toronto (Mineau et al. 2018), while the prevalence of MRSA has decreased in Spain (Martínez Pérez-Crespo et al. 2021). In our study, we noted a significant decrease in the prevalence of MRSA in our ICUs over the study period, while overall, the prevalence of all other phenotypic resistant Gram-negative bacteria increased significantly.

According to the SENTRY study, BSIs caused by MRSA were seen among patients in the non-ICU setting, while VRE, ESBL-positive Klebsiella sp., carbapenem-resistant Klebsiella sp., and E. coli were more common among patients in ICUs (Pfaller et al. 2020). In the US, the prevalence of MRSA was higher in ICU patients (Ham et al. 2020). In our study, there was no statistically significant difference in the prevalence of VRE, although MRSA was significantly more common in ICUs than in the hospital wards. Our study found the rate of antibiotic-resistant isolates to be generally higher in ICUs than in hospital wards. ICUs are units where resistant infectious species and critical patients are monitored and treated; furthermore, these dedicated areas frequently require invasive interventions. Therefore, the likelihood of encountering resistant bacteria here is higher than in other hospital wards.

In a study conducted in the USA, the incidence of MRSA per 10,000 bed days was reported to have decreased (Jernigan et al. 2020). In a study from China, the incidence of Gram-positive microorganisms in BSI per 1,000 admissions had decreased (Zhu et al. 2018). In another study from China, a detected increase in the incidence of Gram-negative microorganisms was not considered statistically significant (Zhu et al. 2021). The incidence density increased linearly in a medical-surgical intensive care unit during 2005–2007 in Turkey (from 3.57 to 9.60 per 1,000 patient-days) (Erdem et al. 2009). The incidence of BSI in our hospital over the 12 years was 20.8/10,000 bed days and 10.2/1,000 admissions. In our study, the correlation of phenotypically resistant bacteria with 10,000 hospital bed days and 1,000 hospital admissions was examined, and an inverse correlation was found in MRSA isolates only for both 10,000 bed days and 1,000 admissions.

In conclusion, although our study was conducted at only one healthcare center, our hospital is a tertiary hospital and the largest in the South Marmara region of Turkey. While our contamination rate is high, the prevalence of polymicrobial growth and CoNS has decreased significantly over the years. However, although the frequency of S. aureus and MRSA has decreased significantly in ICUs, the prevalence of K. pneumoniae increased. The most important finding of this study was the dramatic increase in carbapenem and colistin resistance in recent years. Our infection control committee has been operating since 1995. We have blood culture collection procedures, and we use regular educational interventions for proper blood culture specimen collection for physicians, nurses, and phlebotomists. We have a hand hygiene policy, infection control education and procedures, and antimicrobial stewardship policies (restriction for broad-spectrum antibiotics, cumulative antibiogram, following usage of antibiotics by defined daily doses, de-escalation, and stop order). In order to prevent the spread of K. pneumoniae and other resistant bacteria, we are trying to increase hand hygiene compliance rates by constantly repeating hand hygiene training. Physicians can use broad-spectrum antibiotics (such as carbapenems and polymyxins) only with the approval of infectious diseases and clinical microbiologists (restriction policy). We believe we need to re-evaluate our hospital’s hand hygiene policy, infection control procedures, and antimicrobial stewardship. On the other hand, physicians should be aware of the increasing drug resistance, such as ESBL and carbapenem resistance, and choose their empiric treatment according to susceptibility patterns. We believe that monitoring the distribution of pathogens and antibiotic susceptibility profiles at regular intervals, especially in ICUs, will contribute to our understanding of the increase of resistant microorganisms and help prevent their spread with antimicrobial stewardship and infection control policies.