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
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.
This single-center study was conducted at an 880-bed tertiary care university hospital, per the principles of the Declaration of Helsinki. Our hospital was accredited by Joint Commission International two times (2007–2010 and 2012–2015) in the past. Approval was granted by the Ethics Committee (2021–11/6).
This study was a retrospective analysis of all data from blood cultures carried out by the Microbiology Laboratory from January 2008 to December 2019. We evaluated all BSI data without distinguishing between community-onset or hospital-acquired infections because separation in the BD EpiCenter™ data management system (Becton Dickinson, USA) is not very credible. Blood culture specimens from adult (> 18 years) patients from hospital wards and intensive care units (ICU) were evaluated. The study was divided into four-time intervals (2008–2010, 2011–2013, 2014–2016, 2017–2019) to track the distribution of microorganisms and changes in antimicrobial resistance and compare between periods during the 12 years. Patient data were obtained from the BD EpiCenter™ data management system. Our study did not include molecular data on resistance profiles. To avoid duplication from the same patient, if the same organism caused persistent BSIs, only one specimen from the first episode within 30 days, was included for each patient in the study. Each infection was considered individually if patients had two or more separate BSIs. Patients below 18 years of age and outpatients were excluded from the study (Zhu et al. 2018).
Guidelines from the Center for Disease Control and Prevention (CDC) were followed to distinguish true BSI agents from contamination. Causative agents for BSIs were considered to be either pathogenic microorganism growth detected in one or more blood cultures or the identical skin microbiota isolates [diphtheroids (
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;
Distribution of microorganisms in bloodstream infections in the wards and intensive care units.
Bloodstream infection episodes | Wards n (%) | Intensive care units n (%) | Overall n (%) | |
---|---|---|---|---|
Monomicrobial | Gram-negative | 3,065 (42.8%) | 710 (40.9%) | 3,775 (42.5%) |
971 (13.6%) | 57 (3.3%) | 1,028 (11.6%) | ||
529 (7.4%) | 146 (8.4%) | 675 (7.6%) | ||
261 (3.6%) | 186 (10.7%) | 447 (5.0%) | ||
275 (3.8%) | 65 (3.7%) | 340 (3.8%) | ||
Gram-positive | 2,289 (32.0%) | 441 (25.4%) | 2,730 (30.7%) | |
Coagulase-negative staphylococci | (717 10%) | (10.6184 %) | (10.1901 %) | |
717 (10%) | 96 (5.5%) | 813 (9.1%) | ||
188 (2.6%) | 57 (3.3%) | 245 (2.8%) | ||
191 (2.7%) | 38 (2.2%) | 229 (2.6%) | ||
Fungi | 559 (7.8%) | 106 (6.1%) | 665 (7.5%) | |
Monomicrobial (Total) | (5,913 82.7%) | (1,257 72.3%) | (7,170 80.6%) | |
Polymicrobial | 1,240 (17.3%) | 481 (27.7%) | 1,721 (19.4%) | |
Total | 7,153 (100%) | 1,738 (100%) | 8,891 (100%) |
In the analysis of monomicrobial growths,
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
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
The most common microorganisms in all positive blood cultures over the 12 years.
Frequency of microorganisms within all positive blood cultures over the 12 years.
VRE – vancomycin-resistant enterococci, MRSA – methicillin-resistant
Tables II and III show the resistance rates of the most common bacteria at different points during the 12 years. In
When we investigated Gram-positive bacteremia, daptomycin, vancomycin, and linezolid-resistant
Antibiotic resistance rates of the most common Gram-negative bacteria in blood cultures.
Wards | ICU | Overall | Wards | ICU | Overall | Wards | ICU | Overall | Wards | ICU | Overall | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Ceftriaxone | 25.7 | 23.8 | 25.6 | 0.664 | 38 | 50.4 | 41.1 | <0.001 | 38.2 | 28.5 | 33.4 | 0.002 | - | - | - | |
Cefotaxime | 11.3 | 23.8 | 12.3 | <0.001 | 10.7 | 20.2 | 13.1 | <0.001 | 32.6 | 43.5 | 38 | 0.001 | - | - | - | |
Cefepime | 36.9 | 49.5 | 37.9 | 0.010 | 46.8 | 67.2 | 52 | <0.001 | 47.7 | 62.5 | 55 | <0.001 | 19.3 | 38.2 | 24.8 | <0.001 |
Imipenem | 1.4 | 1 | 1.3 | 0.589 | 25.1 | 48.9 | 31.1 | <0.001 | 74.9 | 88.7 | 81.7 | <0.001 | 23.9 | 39.4 | 28.4 | <0.001 |
Meropenem | 0.9 | 1 | 0.9 | 0.620 | 24.7 | 48.9 | 30.8 | <0.001 | 74.7 | 90.7 | 82.6 | <0.001 | 17.8 | 34.1 | 22.6 | <0.001 |
Ertapenem | 2.9 | 4.8 | 3.1 | 0.219 | 25.6 | 46.6 | 30.9 | <0.001 | 76 | 74.3 | 75.2 | 0.558 | 77.3 | 77.1 | 77.2 | 0.946 |
Piperacillm- Tazobactam | 23.8 | 25.7 | 24 | 0.663 | 50.5 | 72.5 | 56.1 | <0.001 | 50 | 66.7 | 58.2 | <0.001 | 15.6 | 31.2 | 20.2 | <0.001 |
Amikacin | 1.4 | 1.9 | 1.4 | 0.438 | 5.6 | 21 | 9.5 | <0.001 | 70.4 | 76.2 | 73.2 | 0.053 | 5.4 | 8.2 | 6.2 | 0.265 |
Gentamicin | 26.1 | 36.2 | 26.8 | 0.024 | 23.3 | 42.7 | 28.2 | <0.001 | 62.2 | 75.2 | 68.6 | <0.001 | 12.2 | 26.5 | 16.4 | <0.001 |
Colistin | 0.2 | 1 | 0.3 | 0.275 | 6 | 14.1 | 8.1 | <0.001 | 2.3 | 1.4 | 1.8 | 0.477 | 0.7 | 1.2 | 0.9 | 0.633 |
Fosfomycin | 0 | 0 | 0 | - | 0.8 | 1.1 | 0.9 | 0.411 | 1.6 | 0.9 | 1.3 | 0.570 | - | - | - | - |
Ciprofloxacin | 44.6 | 44.8 | 44.6 | 0.978 | 37.2 | 69.8 | 45.5 | <0.001 | 81.2 | 96.8 | 88.9 | <0.001 | 11.2 | 20 | 13.8 | 0.008 |
ESBL | 36.6 | 43.8 | 37.1 | 0.086 | 45.9 | 56.9 | 48.7 | 0.001 | - | - | - | - | - | - | - | - |
Carbapenem- resistant | 3.3 | 4.8 | 3.5 | 0.294 | 29.8 | 58.4 | 37.1 | <0.001 | 90.5 | 93.8 | 92.1 | 0.080 | 83.4 | 88.2 | 84.8 | 0.162 |
ESBL - extended-spectrum ß-lactamase, - - not tested
Antibiotic resistance rates of the most common Gram-positive bacteria in blood cultures.
Wards | ICU | Overall | Wards | ICU | Overall | Wards | ICU | Overall | ||||
Daptomycin | 0 | 0 | 0 | – | 0 | 0 | 0 | – | –1 | –1 | –1 | – |
Oxacillin | 16.6 | 37.7 | 19.7 | < 0.001 | 82.9 | 90.1 | 84.7 | 0.001 | –1 | –1 | –1 | – |
Vancomycin | 0 | 0 | 0 | – | 0 | 0 | 0 | – | 10.9 | 8.1 | 10.1 | 0.185 |
Teicoplanin | 0.8 | 0.7 | 0.8 | 0.668 | 6.5 | 9 | 7.1 | 0.155 | 10.4 | 8.1 | 9.7 | 0.273 |
Linezolid | 0 | 0 | 0 | – | 0.7 | 0.6 | 0.7 | 0.624 | 1 | 1.1 | 1.1 | 0.587 |
Penicillin | –1 | –1 | –1 | – | –1 | –1 | –1 | – | 38.8 | 26 | 35.4 | < 0.001 |
High-gentamicin level | –2 | –2 | –2 | – | –2 | –2 | –2 | – | 43.5 | 48 | 44.7 | 0.202 |
1 – not determined, 2 – not tested
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 (
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.
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
According to the SENTRY study, BSIs caused by MRSA were seen among patients in the non-ICU setting, while VRE, ESBL-positive
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