Review Findings on E. coli Bacteremia

Data presentation

This chapter is dedicated to analyze the data of the selected articles based on the research question and the inclusion and exclusion criteria with the aid of the Joanna Briggs Institute reviewer’s protocol. According to the JBI approach, it is essential on the part of the researcher, at the time of data analysis to formulate an accurate presentation of the results with the aid of charts, a draft diagram, figure, or table to introduce the findings (Munn, et al. 2019). It is also suggested that the researchers do design cautiously how they plan to introduce the information separated from the assortments of scientific evidence. Arranging at this stage is based on the process, studies that met the pre-determined inclusion/exclusion criteria, and answer the research question were included. This procedure might be additionally refined during the audit procedure as the analysts increment their mindfulness and thought of the substance of the entirety of their included sources. In accordance with the protocol, the 15 articles that have met the PICO and inclusion criteria were screened by authors from the exploration of varied reasons in the development of Escherichia coli bacteremia among the populace. These particular studies were considered for the review as it detailed or critically analyzed about several risk factors behind the most commonly caused E. coli bacteremia among the population. The findings of the investigations were connected to look into the development of E. coli bloodstream infection and it’s associated with all causal relationships. Therefore, the data findings are considered to be suitable as the study matched with the inclusion and exclusion criteria set for this review purpose. The main results will be presented in this chapter without analysis. It will validate the main outcomes and focus on the indication essentially needed to respond to the research question. The chapter will demonstrate the list of articles that were included in the study and the study design (Refer to Table 3.1).

The most used databases in the field of nursing and healthcare are MEDLINE and CINAHL and therefore searches were carried out within these databases. Below is the list of required research investigations included within the review:

The overall summary of all the listed papers included will demonstrate a thorough understanding of the literatures (Table 3.2). It will provide critical appraisal of the chosen articles by setting out the research method used in each article, the main findings, their strengths and weakness.

Critical Evaluation of articles

Considering different types of evidence to answer a research question is really important as some of the information in the article might be relevant while others might not match appropriately with the pre-determined inclusion and exclusion criteria for the investigation. It is therefore very crucial to evaluate the quality of the literature. This will help to evaluate and measure the article to see if it meets the required validity, credibility, the significance of the findings, the generalization of the data, and the study feasibility based on the study design to be included in the study for answering the focused research question (Aveyard, 2014).

Based on the JBI approach, each article was rated on a scale ranging from 1(very weak) to 5 (very strong) (Table 3.3). This tool critically evaluated the studies using the checklist-style method for assessing the quality of each paper.

The key elements that were scrutinized in the above studies were study design, study methods, and outcomes. Grove, Burns, and Gray (2013) believed that while appraising evidence these elements must be included. Whereas Aveyard, (2014) mentioned that when the strength and weaknesses are considered, it is easy to identify whether the article will contribute to answer the research question. Conversely, Greenhalgh, (2010) stressed to focus on the methodology of the study to identify if there is any flaw.

Summary of Included Articles

The main categories of studies that were included in this study were prospective case-control study, case-control study, prospective survey, cohort study, multicentre cohort investigation, retrospective investigation, prospective observational investigation, retrospective chart audit of adult patients, systematic review or audit, and review study (Table 3.4). The aim is to provide a synopsis of the features of these studies.

Summary of Articles based on study designs and their findings

Prospective Case control investigations:

The investigation conducted by Abernethy, et al., 2015 was a Prospective Case-control investigation. The study conducted a national mandatory surveillance scheme within the time frame of 1 July 2011 to 30 June 2012. The sample size of the participants was 32, 130 cases. This was the primary national investigation of death induced by E. coli bacteremia among patients within England. The researchers embraced a huge national investigation with an objective to distinguish the potential hazard factors for the one-month all-cause mortality among the bacteremia caused by E. coli within the study patients. The findings of the enormous study were analyzed using the multivariate logistic regression to recognize the potential factors using the statistical tool. The potential findings of the study were 5220 mortality among 28, 616 bacteremia patients caused by E. coli. A death rate of 18.2% (95% CI 17.8–18.7%) was reported by the researchers. 75% of mortality was observed inside two weeks of sample assortment. Factors connected independently with the expanded rate of mortality were: age < 1 year or > 44 years; a hidden respiratory or obscure infection; resistance to antibiotic ciprofloxacin; infection acquired from the hospital not being conceded; and bacteremia commonly observed during the winter season. The gender female and the urogenital concern were related to a decrease in the mortality rate (Abernethy, et al., 2015). Similarly, the study conducted by authors Bou-Antoun, et al., 2016 was a Prospective Case-control investigation over a period of 24 months from April 2012 to March 2014 with a total number of 66,512 of bacteremia cases caused by E. coli. The details of the cases were obtained from the national mandatory surveillance database and the findings of the antimicrobial sensitivity and resistance were correlated with the available data on LabBase2 which is a voluntary nationwide database on microbiological details. This particular investigation detailed that the incidence rate of the malady expanded by 6% from 60.4 / 100,000 populace within 2012 - 2013 to 63.5 per 100,000 populace in 2013–14. The paces of bacteremia by E. coli differed with considering parameters such as sex and age, with 70.5% (46,883 out of 66,512) of cases found among patients of age  ≥ 65 years and 52.4% (33,969 out of 64,846) of cases of gender female. The most widely recognized hidden reason for bacteremia was the disease of the genital/urinary tract (41.1%; 27,328 out of 66,512), of which 98.4% (26,891 out of 27,328) were attributed to infection of the urinary tract (UTIs). Most of the cases (76.1%; 50,617 out of 66,512) demonstrated positive cultures of blood previously or inside 2 days of affirmation and were named community-onset cases. Anyway, 15.7% (10,468 out of 66,512 cases) happened among patients who were admitted to the hospital for longer than seven days. Culture showed non sensitivity to ciprofloxacin, piperacillin-tazobactam, third-generation cephalosporins, gentamicin and carbapenems were 18.4% (8,439 out of 45,829), 10.4% (4,256 out of 40,734), 10.2% (4,694 out of 46,186), 9.7% (4,770 out of 49,114) and 0.2% (91 out of 42,986), individually. Resistance to anti-microbial agents was higher among emergency clinic onset cases than for those introducing from the community (for example resistance against ciprofloxacin was 22.1% (2,234 out of 10,105) for hospital-onset versus 17.4% (5,920 out of 34,069) for the community-acquired cases). All the data is considered to be statistically validated having p < 0.0001 (Bou-Antoun, et al., 2016). In this regard the examination conducted by Ikram, et al., 2015 was also a case-controlled investigation 76 prospective case and 156 were considered as controls which were introduced within the study. All the study members were 65 years or older than that. The findings were analyzed using multivariate analysis the hazard factors that showed a statistical correlation with the development of E. coli infection were the gender female (altered Odds Ratio 3.2; 95 % confidence interval 1.5–6.9); the degree of care (high dependency OR 7.5; 2.2–25.7) when the data was compared with living alone; resistance to antibiotics by MDR E. coli in the hospital setting (OR 5.6; 2.5-12.9). All the findings were considered significant if the p-value is 0.05 (Ikram, et al., 2015). Moreover, Trecarichi, et al., 2019 also reported via prospective case studies from January 2016 to December 2017 with 342 cases of E. coli induced bloodstream infections that the resistance to the 3rd generation cephalosporin was found to be 25.7%. After statistical analysis of the study the factors such as a recent procedure on endoscopy, culture-positive rectal swab for MDR E. coli, the prophylaxis of antimicrobial agents, and the long associated neutropenia were found to be in independent association with the 3rd generation cephalosporin-resistant E. coli. The researchers also stated that the one-month mortality rate was found to be 7.1%. Therefore, the statistical Cox regression analysis revealed that the causal factors behind the mortality were a liver failure, septic shock, gender male, relapse phase of HM, and resistance developed by the culture bacterium E. coli against 3rd generation cephalosporin (Trecarichi, et al., 2019). Another prospective case-control study conducted by Blandy, et al., 2019 of all the positive cases of E. coli induced bloodstream infections in between the time span of 2011 to 2015. The findings of the investigation highlighted that the number of cases of bloodstream infections caused by E. coli had expanded to 76% within the period of the study. Among them, most of the cases were referred to as community-acquired. A study on the antimicrobial resistance revealed that resistance was developed and augmented against the aminoglycosides, 3rd generation cephalosporins, and quinolones within the period of study among both hospital and community-acquired cases. Therefore, the study identified the potential hazard factors to be the prolonged stay at the hospital and development of resistance against the 3rd generation cephalosporins and quinolones along with elderly age. The mortality rate had expanded from 7% to 12% from the 7th day to the 30th day of the investigation respectively (Blandy, et al., 2019). The ultimate study that would be considered within this study design is conducted by Denis, et al., 2015 from January 2005 to December 2009 (5 years) with only adult cases that had demonstrated positive blood culture with ESBL EC. The findings of the investigation highlighted that the predominance of ESBL EC bloodstream infection had expanded from 5.2% in the year 2005 to 13.5% in the year, 2009 with statistical significance of p values < 0.003. When the researchers categorized the types of strains of ESBL positive cultures, 70% of them represented the CTX –M types. When the data were analyzed and adjusted the potential risk factor for bloodstream infection caused by ESBL EC were the previous infections or colonization with the same bacteria. The results had the statistical validation of odds ratio 11.3, 95% confidence interval 1.2 - 107; p-value = 0.003. The study highlighted that the previous antimicrobial therapy was not adequate for the infection caused by the same ESBL positive EC group with statistical validation of 48% vs. 85%; p-value = 0.003. However, the researchers did not find any association in between the prolonged duration of hospital stay with ESBL positive EC infection having a p-value of 0.088. Another important finding was the one-month mortality was found to be raised but not that much significant in between the two categorized gatherings (30% versus 27%; p-value = 0. 82). Moreover, patients who had extreme basic comorbidities such as hematological sickness were noted among 68% (28) of the cases; extreme forms of neutropenia was noticed among 27% of the patients (ANC 100/mm3); about 50% of the patients had undertaken chemotherapy within their last month. The mean of the Acute Physiology and Chronic Health Evaluation (APACHE) score was found to be high among the two gatherings with P values of = 0.8. In addition, this, in the case of ESBL positive EC and non-ESBL positive EC nearly 83% and 71% of the cases were found to be hospital-acquired and there was no such significant difference observed in between the two groups having the statistical significance of (p = 0.27) (Denis, et al., 2015). However, there are few constraints with regard to the investigations conducted with the above-mentioned study designs are not all patients were followed up and the statistical analysis model had revealed considerable missing presentation data with the relapse examination. Despite the fact that the sample size and the findings analyzed along with the information index gathered to give some trust in the impact gauges. Moreover, not all factors of intrigue were accessible (for example co-morbidities). Therefore, future study or research is required as suggested by the researchers to increase a more noteworthy understanding of these infections and to distinguish particular territories for intercession. As few studies were carried out within a country with an expanded rate of 3rd generation cephalosporin resistance therefore the findings could not be generalized. In addition to this, the researchers demanded further study within this field with respect to the community-acquired cases (Abernethy, et al., 2015; Denis, et al., 2015; Bou-Antoun, et al., 2016, Blandy, et al., 2019).

Cohort Investigations:

The investigation conducted by authors, Cornejo-Juárez, et al., 2016 was a cohort investigation based on a cancer referral hospital. The study included patients suffering from hematologic malignancies who got admitted to the hospital before the first cycle of chemotherapy. About 126 patients who have been recently diagnosed with hematologic malignancies were included within the investigation. The findings of the study highlighted about 126 patients who have been recently diagnosed with hematologic malignancies. The study categorization highlighted that out of total samples 63 has been characterized as colonized or infected with ESBL positive EC and another 63 patients are infected by non-ESBL positive EC. The age of the study participants was within 42 ± 16 years and among them 78% were males. It was also observed that 22.2% or 14 patients were suffering from BSI due to ESBL positive EC and 4.7% or 3 patients suffered from BSI due to non- positive ESBL-EC. The researchers also highlighted that the risk of infection has augmented with the infection by positive ESBL-EC having relative risk (RR) = 3.4, 95% confidence interval (95% CI) 1.5-7.8, p = 0.001; the mortality time was also found to be less (74 ± 62 vs. 95 ± 83 days, p < 0.001) with more number of days at hospital (64 ± 39 vs. 48 ± 32 days, p = 0.01). The financial expenditure associated with higher rate of infection were $6528 ± $4348 versus $4722 ± $3173, p = 0.01. However, the researchers also stated that there was no such significant difference with regard to the overall rate of mortality in between both the groups (Cornejo-Juárez, et al., 2016). Similarly, another examination conducted by Baudron, et al., 2014 was a multi-centered cohort study that included young participants (N = 395) within the age range of 18-64 years; adult or elderly participants (N = 372) within the age range of 65-79 years; extremely old categorized participants above the age of 80 years (N = 284). Within the examination, the researchers also calculated the risk factors in terms of medical and bacteriological for mortality with respect to each of the groups via logistic regression and multivariate analysis within each of the gatherings. The investigation highlighted that the category of the young and the elderly patients were suffering from varied co-morbidities in comparison to the very old category of participants. The statistical validation of the comorbidities was found to be comorbidity score: 1•5 ± 1•3 and 1•6 ± 1•2 vs. 1•2 ± 1•2, respectively; with P values < 0•001. The category of the young and the elderly patients were suffering more from the hospital-acquired infections with statistical validation of (22•3% and 23•8% versus 8•8%, respectively; having P-value < 0•001). The old-age patients category have shown the extreme worse status of prognosis with a mortality rate of 16•4% versus 10•4% for the category of young patients and 12•0% for the extreme old category of patients with P-value within the range of P = 0•039 respectively (Baudron, et al., 2014). Among the 15 investigations screened, the examination conducted by Lillie, et al., 2019 was a prospective cohort study from 1st November 2017 to 30th April 2018. The investigation included a total of 195 cases of which 188 cases participated ultimately within the process. The findings of the examination highlighted that out of 195 cases, 188 cases have participated within the study. An empirical study on resistance developed against antimicrobials demonstrated that 30.9% of the cases had revealed in vitro resistances. The rate of death within 30 days was found to be 23.6% and the median of the total length of stay at the hospital was found to be 7 days. When the data were analyzed using the multi-variable statistical analysis, the mortality rate within one month was found to be associated increased Charlson score, expanded respiratory rate, raised level of serum urea, residency at home, whereas the study linked the prolonged duration of stay at the hospital with bloodstream infections caused by specifically E. coli. Among the study population 50 patients had acquired BSI due to the following healthcare issues such as the utilization of urinary catheters, complications developed due to antibiotic therapy, or any surgical procedures (Lillie, et al., 2019). Another study that can be discussed here was conducted by Rosa, et al., 2014. It was carried within a single tertiary care hospital within the time span of October 2009 to August 2011. The investigation included all the successive stable hemodynamically malignant patients who were older than 18 years of age and therefore got admitted to the hematological ward of the hospital. Overall 307 adult malignant cases of FN were incorporated within the study. The findings of the study highlighted that overall 307 adult malignant cases of FN were incorporated within the study. Among them, the study analyzed that 115 cases were suffering from bloodstream infections and it was documented. When the outcomes were analyzed using the multivariate analysis it was observed that polymicrobial bacteremia was highly co-related with septic shock with a statistical significance of P = 0.01. The bacteriological data identified that the specific blood cultures which had an independent association with the septic shock were streptococci having a P-value of 0.02 and Escherichia coli having a P-value within 0.01. Therefore the findings highlighted that the malignant patients with neutropenia associated with polymicrobial bacteremia or bloodstream infections with culture Streptococci or E. coli were at expanded risk of septic shock at the time of FN (Rosa, et al., 2014). The researchers of the few studies had highlighted that further study is required as this might not even reduce the existing or growing number of cases of E. coli induced bloodstream infections. They stated that a lower association was found with bacterial cultures namely Pseudomonas aeruginosa and Staphylococcus aureus which are frequently responsible for the worsening condition of septic patients. Therefore they had shown caution with regard to the generalization of the data. Moreover, the researchers had also stated that the investigation was prone to bias as observed within observational investigations. However, they had taken precautions to minimize the systemic errors within the study (Rosa, et al., 2014; Lillie, et al., 2019; Baudron, et al., 2014).

Retrospective Investigations:

The first examination that would be discussed under this study design section was conducted by Burnell, et al., 2019 in between October 2016 to April 2018 with a total of 214 elderly patients cases of bloodstream infected patients who were admitted to the hospital were included within the study. The cohort study outcomes highlighted the hazard factors for bloodstream infection are the ESBL positive cultures (with Risk Ratio of RR = 5.9); undergoing antibiotic therapy within the last six months, RR = 2.3. It was observed that those patients who were suffering from bloodstream infections caused by ESBL positive cultures were hospitalized for a prolonged duration having a mean value of 16 days vs. 6 days for non-ESBL. They also received a longer duration of antibiotic therapy (11.7 days versus 5.3 days) and had undergone varied therapy of antibiotics within the last half a year (1.9 vs. 0.7). When the study was investigated using the multivariate statistical analysis tool it demonstrated that the history of the previous infection by the strains of ESBL (OR 14.7, CI 1.8–120) along with expanded use of antibiotics within the last 6 months having statistical validation of (OR 4.3, CI 1.7–11.2). Therefore, these two parameters were considered as potential hazard factors for bloodstream infection (Burnell, et al., 2019). Another study that falls under the study design was carried out by Siritip, et al., 2019. The total number of 171 kidney transplants patients was included within the study. The patients had acquired bloodstream infections within the first year of the surgical process within the time span of January to December 2016. The major findings highlighted that a total of 26 cases or 15.2% suffered from bloodstream infections among the total number of 171 kidney transplants patients. Among them 58.5% of the populace were of the male gender, having the age mean within 43 ± 12 years as mean ± SD. The maximum number of patients who had undergone the deceased-donor allograft was 58.5% and 59% of them received the induction therapy. The analysis with the Kaplan–Meier tool demonstrated that 12.3% of the cases had developed bloodstream infections within three months, 13.5% within six months, and 15.2% within the 12 months following kidney transplantation. The bacteriological data on the bloodstream infection revealed that 92% of the cases were infected with culture E. coli. E. coli was found to be the most frequent pathogen (nearly 65%) for the cases of bloodstream infections and 71% of the cultures were found to be ESBL positive. Most of the cases of bloodstream infections have originated from the genitourinary tract infections of about 85%. When the findings were analyzed using the multivariate analysis it was found that the second time kidney transplantation having the (HR, 4.55; 95% CI, 1.24–16.79 (P-value =0.02) and the individuals receiving the induction therapy (HR, 3.05; 95% CI, 1.15–8.10 (P-value 0.03) were found to have a strong correlation with bloodstream infections. It was also highlighted within the study by the researchers that only one patient (4%) had acquired an acute form of cellular rejection and again one patient (4%) suffered death due to septic shock (Siritip, et al., 2019). The final study that will be discussed under this section was conducted by Tuon, et al., 2014 for the time span of January 2009 to January 2011. The clinical records of 88 adult patients suffering from hospital-acquired E. coli bloodstream infections were analyzed. The study findings highlighted that it has enrolled 88 patients for the investigation. The median of the length of stay at hospitals was 16 having the interquartile percentiles in the range of 25% and 75% individually. The mean of the age was found to be 59.7 ± 17.3 (range = 18 –96) years and among them 52.3% were females. Nearly 8% of the cases were suffering from ESBL positive EC infection, the overall length of stay at the hospital was 24.6 ± 24.0 days. Maximum of the patients had anemia with a mean hemoglobin value of 10.3 ± 2.3 g/L; the raised level of immature cells (17.8 ± 14.7%), leukocytosis (14.3 ± 11.8 × 109/L), kidney impairment, and hiperbilirrubinemia. The univariate analysis demonstrated that the varied hazard factors such as persistent kidney impairment, the altered status of a psychological condition, leukocytosis, and the Charlson index for the comorbidities had an association with the death rate whereas multivariate analysis revealed that the altered status of mind can be a strong risk factor for death among patients suffering from ESBL positive EC bloodstream infections (Tuon, et al., 2014). Certain investigations could not effectively distinguish the raised or the lowered level of the hazard factors for the bloodstream infections caused by ESBL positive cultures. The researchers demanded further study to correlate the antibiotic therapy with bloodstream infection caused by ESBL positive cultures. Another point with regard to limitations is a single center investigation might not properly correlate the factors so the researchers demanded further broader investigation (Tuon, et al., 2014; Burnell, et al., 2019).

Systematic Reviews:

Jones, et al., 2019 conducted a systematic review with the populace of elderly adults of all settings who are infected with E. coli causing bloodstream infections. The study incorporated all types of conduct interventions within the investigation and specified about the categories of care settings for instance care homes, secondary care, community center, and the long time or end of life care centers. The study inclusion criteria allowed the incorporation of all full-length peer-reviewed communication from the year 1990 on the topic matching with the research questions. However, as per the exclusion criteria studies on asymptomatic bacteriuria, studies with not specified about the age of the participants clearly and also those investigations which were conducted within specialized units such as ICU, burn units having old age patients suffering from varied intense comorbidities were excluded from the study investigation. Moreover, studies on any pharmacological interventions were also excluded from the study. Finally, after the strict screening of the studies on the basis of inclusion and exclusion criteria, a total of 21 studies were thought though they also demonstrated the absence of the quality of the methodology. Among the interventions 6 multi-faceted hospital-based interventions were discussed which incorporated education and that with the aid of reviews or feedbacks diminished the cases of urinary tract infections, however, only 3 investigations could show the statistical validation. 1 investigation highlighted about the diminished level of catheter utilization causing UTI (CAUTI) by nearly 88% having statistical validation of (F (1, 20) = 7.25). In this regard, another investigation also reported about the lowering value of CAUTI at the time of phase I of the study from value 11.17 to 10.53 and during Phase II it lowered by 0.39 (χ2 = 254). Similarly, another study also reported about the fewer cases of UTI in terms of per patient week having a risk ratio of 0.39. Moreover, another two studies conducted online training on catheter insertion and care models reduced the number of CAUTI cases from the value of 33 to 14 and also from 10.40 to 0. The study findings also highlighted that with the enhancement or raised level of the healthcare practitioners, the community continence medical professionals and removal of the urinary catheter helped to lower down the rate of bloodstream infection by E. coli (Jones, et al., 2019). Another single study that would be discussed was conducted by Poolman, et al., 2018 with the old age populace and the individuals who were undertaking certain procedures were the target populace of this study. It highlighted on the hazard factors contributing to the hospital-acquired bloodstream infections caused by the two most frequent bacteria named E. coli and Staphylococcus aureus. The study audit also discussed about the factors that resulted in the treatment of bloodstream infections very difficult as a result of expanding antimicrobial resistance. The essential findings of the study highlighted that routine administration of S. aureus and E. coli vaccinations among the old age populace and the individuals who were undertaking certain procedures associated with expand risk of infection could hinder a certain portion of the disease to reach its extremity. The procedure of vaccination would also strongly hinder the development of resistance against antibiotics (Poolman, et al., 2018). With regard to the limitations within the study, the researchers indicated that the protocols concerning the removal of the catheter, enhanced level of staffing, and the education of the patient’s demands further investigation. The review of the study revealed about the heterogeneity of the screened investigations (Poolman, et al., 2018; Jones, et al., 2019).

By condensing the articles, the main points were summarised and depicted into manageable amount.

Main Themes

It is important to code and classify the data into themes using thematic analysis method. This will further help to methodologically analyse the data in the next chapter (Table 3.5) (Ibrahim, 2012).

Therefore the following screened investigations were analyzed using the Joanna Briggs Institute reviewer’s protocol. According to this particular JBI approach, it is essential on the part of the researcher, at the time of data analysis to formulate an accurate presentation of the results with the aid of charts, a draft diagram, figure, or table to introduce the findings (Lockwood et al. 2019). The results were analyzed using the thematic analysis protocol. From the data analysis six thematic groups have been generated namely (Refer Table 3.5):

Growing Antimicrobial Resistance

An investigation was conducted by authors Abernethy, et al., 2015 on the exploration of varied reasons behind the mortality rate because of Escherichia coli bacteremia among the populace of England. This particular study critically analyzed about several risk factors behind the most commonly caused E. coli bacteremia among the population. The factor connected independently with the expanded rate of mortality was resistance to the antibiotic ciprofloxacin. The other studies conducted by Bou-Antoun, et al., 2016; Ikram, et al., 2015; Trecarichi, et al., 2019; Lillie, et al., 2019; Burnell, et al., 2019; Blandy, et al., 2019; Rosa, et al., 2014; Denis, et al., 2015; Poolman, et al., 2018 also highlighted about the growing perils of antimicrobial resistance for the blood stream infection caused by bacterium E. coli. Study conducted by Bou-Antoun, et al., 2016 clearly highlighted about culture showing non sensitivity to ciprofloxacin, piperacillin-tazobactam, third-generation cephalosporins, gentamicin and carbapenems were 18.4% (8,439 out of 45,829), 10.4% (4,256 out of 40,734), 10.2% (4,694 out of 46,186), 9.7% (4,770 out of 49,114) and 0.2% (91 out of 42,986), individually. Resistance to anti-microbial agents was higher among emergency clinic onset cases than for those introducing from the community (for example resistance against ciprofloxacin was 22.1% (2,234 out of 10,105) for hospital-onset versus 17.4% (5,920 out of 34,069) for the community-acquired cases).

Infection or colonization with Extended spectrum beta lactamase strain of E. coli:

Extended-spectrum beta-lactamase is the potential enzyme proteins coded by certain bacteria that offer them resistance to the commercially available beta-lactam ring containing antibiotics that incorporates monobactam, aztreonam cephalosporins, and the penicillin group of antibiotics. As analyzed from the investigations conducted varied studies such as Cornejo-Juárez, et al., 2016; Burnell, et al., 2019; Siritip, et al., 2019; Denis, et al., 2015; Tuon, et al., 2014 had highlighted about the bloodstream infection caused by these group of bacteria and they are highly associated with mortality of the patients. So it is considered as one of the potential risk factors. A study conducted by Cornejo-Juárez, et al., 2016 highlighted that out of total samples 63 have been characterized as colonized or infected with ESBL positive E. coli. It was also observed that 22.2% or 14 patients were suffering from BSI due to ESBL positive E.coli. The researchers also highlighted that the risk of infection has augmented with the infection by positive ESBL-EC having relative risk (RR) = 3.4, 95% confidence interval (95% CI) 1.5-7.8, p = 0.001. Another study conducted by Burnell, et al., 2019 highlighted about a total of 214 cases of bloodstream infected patients and among them, 14% was due to the ESBL positive cultures. The cohort study outcomes highlighted the hazard factors for bloodstream infection are the ESBL positive cultures (with Risk Ratio of RR = 5.9); undergoing antibiotic therapy within the last six months, RR = 2.3. It was observed that those patients who were suffering from bloodstream infections caused by ESBL positive cultures were hospitalized for a prolonged duration.

Urinary Tract Infection (UTI)

The urinary tract infection is the infection or colonization by the bacteria in the urinary system such as ureters, urethra bladder, and kidneys. Studies conducted by Abernethy, et al., 2015; Bou-Antoun, et al., 2016; Lillie, et al., 2019; Jones, et al., 2019; Siritip, et al., 2019 highlighted UTI as the potential risk factor for bloodstream infection by E. coli. The bacteriological data of the study Siritip, et al., 2019 on the bloodstream infection revealed that 92% of the cases were infected with culture E. coli. E. coli was found to be the most frequent pathogen (nearly 65%) for the cases of bloodstream infections and 71% of the cultures were found to be ESBL positive. Eighty-five percentages of bloodstream infections have originated from the genitourinary tract infections. Similarly, a study by Jones, et al., 2019 also reported cases of UTI in terms of per patient week having a risk ratio of 0.39.

Patients suffering from co-morbidities

Several studies have reported about different types of comorbidities that acted as trigger factors for the bloodstream infection caused by E. coli. The varied comorbidities can be any kind of malignancies, blood disorders, hypertension, diabetes, kidney impairment, old age, immunocompromised status, chronic obstructive pulmonary disorders, etc. So many investigations had supported these causes as potential risk factors for bloodstream infections such as Abernethy, et al., 2015; Trecarichi, et al., 2019; Cornejo-Juárez, et al., 2016; Baudron, et al., 2014; Lillie, et al., 2019; Siritip, et al., 2019; Rosa, et al., 2014; Denis, et al., 2015; Tuon, et al., 2014; Poolman, et al., 2018. The study conducted by Tuon, et al., 2014 focused that maximum of the patients had anemia with a mean hemoglobin value of 10.3 ± 2.3 g/L; the raised level of immature cells (17.8 ± 14.7%), leukocytosis (14.3 ± 11.8 × 109/L), kidney impairment and hiperbilirrubinemia. The univariate analysis demonstrated that the varied hazard factors such as persistent kidney impairment, the altered status of psychological condition, leukocytosis, and the Charlson index for the comorbidities had an association with the death rate whereas multivariate analysis revealed that the altered states of mind can be a strong risk factor for death among patients suffering from ESBL positive EC bloodstream infections.

Prolonged stay at hospital

The long duration of stay at the hospital is a potential risk factor for acquiring bloodstream infections due to multidrug-resistant E. coli. Few investigations conducted by Abernethy, et al., 2015; Bou-Antoun, et al., 2016; Ikram, et al., 2015; Cornejo-Juárez, et al., 2016; Baudron, et al., 2014; Lillie, et al., 2019; Burnell, et al., 2019; Blandy, et al., 2019; Tuon, et al., 2014; Poolman, et al., 2018 had all considered this factor for the pathophysiological condition. A study conducted by Burnell, et al., 2019 strongly highlighted that those patients who were suffering from bloodstream infections caused by ESBL positive cultures were hospitalized for a prolonged duration and belong to the geriatric populace.

Organ transplantation or surgical procedures

Any surgical procedure or organ transplantation causes in the development of weaker immunity due to the associated medications. Investigations conducted by Lillie, et al., 2019; Siritip, et al., 2019 focused that 26 cases, or 15.2% suffered from bloodstream infections among the total number of 171 kidney transplants patients. The maximum number of patients who had undergone the deceased-donor allograft was 58.5% and 59% of them received the induction therapy. The bacteriological data on the bloodstream infection revealed that 92% of the cases were infected with culture E. coli.

Conclusion:

This section demonstrates the main findings of each chosen article. The data is arranged and presented in a tabular format that has portrayed important information. The identified risk factors for E. coli bloodstream infections are growing antimicrobial resistance; infection or colonization with extended-spectrum beta-lactamase strain of E. coli; urinary tract infection; patients suffering from co-morbidities; prolonged stay at the hospital; organ transplantation or surgical procedures. The analysis of these findings will be presented in the following chapter.

Analysis and discussion

The significance of analysis helps the researcher to understand the underlying problems and the existing gaps within the research study on the chosen topic. The findings of the study are merely considered to be facts and figures but the analysis of the figures using an analytical tool helps to comprehend the pattern and area that demands extensive further research to be carried out in the future. Therefore, the process of data analysis helps the researcher to organize the outcomes of the investigations in a structured way and also presents the information which offers context to the research.

Discussion:

As suggested by the 15 scientific pieces of evidence the following factors that have been considered as the major factors for E. coli induced bloodstream infections are growing antimicrobial resistance; infection or colonization with Extended-spectrum beta-lactamase strain of E. coli; urinary tract infection; patients suffering from co-morbidities; prolonged stay at the hospital; organ transplantation or surgical procedures. All these factors have cumulatively contributed towards acquiring and developing the E. coli caused bloodstream infections. Among them, antimicrobial resistance and UTI are considered to be the two most complex factors for E. coli induced BSI. Another study conducted by Abernethy, et al., 2015, had reported that about 50.0% of the patients had suffered from bloodstream infection due to urinary infection source and among few patients had also co-morbidities associated with them such as diabetes. Moreover, it was also reported among studies that the E. coli isolated from the UTI infection, from the samples of urine demonstrated resistance to most of the prescribed potentially strong antibiotics such as co-amoxiclav, amoxicillin, trimethoprim, nitrofurantoin, cefalexin, and ciprofloxacin (Abernethy, et al., 2015). The UK practice guidelines had recommended an empirical therapy for an uncomplicated form of UTI and the urine samples should be collected only form those individuals who did not respond to the treatment or had shown the possible probable failure of treatment, persistent infection, or relapse of the infection after the antibiotic treatment indicating about the resistant species of bacteria. Interestingly investigation among such groups have highlighted that there is a high pattern of bloodstream infections by E. coli among those patients who had suffered from UTI for more than three days. This can be also being referred to as urosepsis. The use of catheter is considered to be a contributing factor for UTI induced bloodstream infection by E. coli (ESPAUR, Report 2017).

Among the other factors that are also considered crucial for the development of UTI by E. coli are the demographic parameters such as the age range specifically within 60 and 75 years having the statistical significance of (p< 0.001; OR = 6.3[2.1–18.9]) (Daga, 2019). According to Owrangi et al., 2018, ExPEC is considered to be an important causative agent for bloodstream infections. Again as per the studies of Jauréguy et al., 2007 and Lefort et al., 2011 both the determinants of the host and bacterial resistance to the antimicrobials immensely impact upon the infection rate. Moreover, this age range is also associated with a high rate of mortality as the immune response is weakened at this age as per the study evidence of Lefort et al. (2011). The study identified varied comorbidities that are associated with expanded risk factors for E. coli induced bloodstream infections are leukocytosis, kidney impairment, and hiperbilirrubinemia. Among the other co-morbidities diabetes is considered to be one of the major factors that predominate among 18.8% of the populace. Studies have also reported a high association in between diabetes and pyelonephritis which expands the risk of infection (Alves et al., 2012). The varied types of malignancies, blood disorders, hypertension, kidney impairment, immunocompromised status, chronic obstructive pulmonary disorders, etc. are also considered to be the significant or potential risk factors for the bloodstream infections caused by E. coli (Tuon, et al., 2014). Moreover, some studies have also reported about the contribution of gastrointestinal infections or complications that might contribute to BSI by E. coli (ESPAUR, Report 2017). A study had also reported that 5 out of 6 patients who were suffering from hepatic cirrhosis has an expanded risk of bloodstream infection caused by E. coli because of the following factors such as the translocation of the bacteria and the altered level of immune response demonstrated by them. Moreover, the study also highlighted that the prolonged stay at the hospital is also considered a potential risk factor for acquiring bloodstream infection due to multidrug-resistant E. coli. Patients staying at the hospital or at the intensive care unit for a prolonged period of time get exposed to multidrug-resistant or extended-spectrum beta-lactamase-producing E. coli (Usein, et al., 2016). Moreover, another study also revealed that individuals who were exposed to hospitals were showing resistance to antibiotic co-amoxiclav with a p-value (p0•0001). Research investigation also revealed that infection due to co-amoxiclav resistant E .coli was showing upsurge with the progress of time of about 11–18% each year (ESPAUR, Report 2017). In this regard, it must be mentioned that the virulence factor of the bacteria has a central role to play to develop infections, and determinations of bacterial determinants will also help to understand and categorize the bloodstream infections. ExPEC bacterial isolates phylogenetic classification has revealed that the two most prevalent groups within the bacteria are B1 (45.8%) and B2 (18.8%) (Usein, et al., 2016; Skjøt-Rasmussen, et al., 2012). If the isolate B1 is present within the bloodstream then it may be capable of causing systemic infections however as per the past literature source group A and B1 are the bacteria that are commensal or intestinal in origin (Usein, et al., 2016; Skjøt-Rasmussen, et al., 2012). However, according to the study conducted by the author, Fratamico et al. (2016), the E. coli of origin group B and D2 are comparatively more virulent strains that might cause infections outside the intestine among both healthy and immune-compromised human beings groups. Only a little information is available about the mechanism of bloodstream infections caused by E. coli, and the bacteria evade the complement system mechanism of the human body with the aid of virulence factors that confers serum resistance such as the traT gene that contributes to virulence factor for bloodstream infections among 85.4% of the E. coli isolates (Micenková, et al., 2017; Miajlovic, et al., 2014). Some group of researchers have investigated about the capsule material that could confer resistance and assist in the survival within the bloodstream this expanding its risk factor and the investigation highlighted that 45.8% of the bacterial isolates that were predominating within the clinical samples having capsules K1 and K5 (Koga et al., 2014; Bozcal et al., 2018; Miajlovic et al., 2016). The polysaccharide compositions of the capsular material are responsible for generating a resistance mechanism against the host immune responses and thereby causing bloodstream infections. Moreover, the urinary tract infection caused by the strains of E. coli consists of a virulence factor named FimH which is considered to be another significant feature of the UTI causing E. coli and these strains are responsible for complicated recurrent infections that result in bloodstream infections later on (Dale, 2015; Laupland, 2013). Another most significant gene among UTI causing E. coli which develops bloodstream infections eventually is papC (Lefort, et al., 2011; Subashchandrabose, 2015). Overall these are all the potential risk factors that might help to develop and acquire the bloodstream infections caused by E. coli as a secondary infection to UTI, gastrointestinal complications, any malignancies or other types of maladies like blood disorders or also due to any surgical procedures or organ transplantation that causes the immune system to become weak against these virulent pathogenic bacteria and might also result in mortality if not treated properly as the case fatality rates are high also among the UK populace.

Conclusion:

The six different emerging themes that were identified from the screened investigations are well supported by most of the studies. Therefore to formulate any intervention to reduce the number of cases of bloodstream infections caused by gram-negative pathogens the following themes should be thoroughly considered.

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