European Journal of Cardiovascular Medicine

In chronic kidney disease (CKD), a variety of pathophysiologic mechanisms are linked to aberrant renal function and a persistent deterioration in the Glomerular Filtration Rate (GFR) [1]. The mortality rate for severe sepsis is higher than 50%. According to WHO, sepsis is defined as a systemic, harmful host response to infection that results in septic shock (severe sepsis and hypotension not reversed with fluid resuscitation) and severe sepsis (acute organ dysfunction secondary to documented or suspected infection). [2,3]

Urosepsis is a type of sepsis originating from a urinary tract infection (UTI) [4]. According to Wagenlehner FM and colleagues (2013), sepsis stemming from infections of the urogenital tract is referred to as urosepsis, which is a well-recognized occurrence that has been reported over the years [5]. Brun-Buisson C. (2000) indicated that the urinary tract is the most frequent source of infection in 20% to 30% of sepsis cases, with urosepsis often arising from UTIs acquired in either community or healthcare settings [6]. The severity of urosepsis is closely tied to the immune function of the patient, similar to other forms of sepsis. Johansen TE and others (2007) reported that among patients with hospital-acquired UTIs being treated in urology departments, the average prevalence of urosepsis was around 12% [7] Bouza E, et al. (2001) noted that in patients with hospital-acquired urinary tract infections (UTIs) treated in various specialties, the incidence of severe sepsis was 2%, while the occurrence of septic shock was 0.3%[8]. Hotchkiss RS, et al. (2003) and Brunkhorst FM (2006) indicated that UTIs contribute to approximately 5%[9] to 7%[4] of deaths caused by severe sepsis. Hotchkiss RS, et al. (2003) highlighted that sepsis results from urinary tract infections, and Brunkhorst FM (2006) specified that urosepsis is a form of sepsis that originates from a urinary tract infection (UTI) [4]. Wagenlehner FM and colleagues (2008) noted that individuals impacted by micro-organisms can trigger inflammation in the urinary system and male reproductive organs [10].

Wagenlehner FM and colleagues (2007) explored the causes of urosepsis. The majority of urosepsis cases are attributed to Gram-negative bacilli [11]. In their research, Wagenlehner FM and associates (2007) noted that the predominant Gram-negative bacilli include Escherichia coli (50%), Proteus spp. (15%), Enterobacter and Klebsiella spp. (15%), and Pseudomonas aeruginosa (5%), while Gram-positive organisms are less commonly involved (15%) [11]. Urosepsis arises from urinary tract infections, and Enterobacteriaceae are the most frequently identified pathogens: 

1. Escherichia coli (52%);
2. Proteus species;
3. Enterobacter species;
4. Klebsiella species;
5. Pseudomonas aeruginosa;
6. Gram-positive bacteria, such as enterococci (5%) [12].

Cek M, et al. (2014) and Tandogdu Z, et al. (2016) noted a rise in sepsis cases linked to fungal organisms, while Gram-positive bacteria have become the leading pathogens overall; however, in urosepsis, Gram-negative bacteria still dominate [13, 14]. According to Cardoso T, et al. (2008), the European Study Group on Nosocomial Infections (ESGNI-004) reported that Gram-positive organisms represented 21.2% of all hospital-acquired urinary tract infections, with Gram-negative organisms comprising 65.9% and yeasts accounting for 12.9% [15]. Cardoso T, et al. (2008) also highlighted that ESGNI-004 found both Candida species and P. aeruginosa were more prevalent in patients with catheters, while E. coli was the most commonly isolated bacterium among catheterized and non-catheterized patients [15]. Tandogdu Z, et al. (2016) emphasized that E. coli remains the most common microorganism. In several countries, some bacterial strains may display resistance or multi-resistance, complicating treatment efforts [14].

Aim and Objectives

1. To study the microbiological spectrum involved in urosepsis among patients with chronic kidney disease (CKD).
2. To study the antimicrobial resistance patterns and treatment of urosepsis in patients with chronic kidney disease (CKD)

The study was conducted in the Department of Nephrology (in the dialysis unit) and Clinical Microbiology of a tertiary care hospital from January 2024 to January 2025 to evaluate the clinic-microbiological spectrum of urosepsis in chronic kidney disease after IEC-HR clearance. It was conducted on 100 patients with chronic kidney disease suffering from urosepsis who were subjected to detailed clinical and laboratory evaluations.

Patients over the age of 18, both male and female, who provided valid informed written consent for the trial and who met the Kidney Disease Improving Global Outcome (KDIGO 2012) criteria for chronic kidney disease (CKD), were included in the study. Patients with HIV, HBsAg, or HCV and who were younger than 18 years old were not included in the study. For all routine blood tests, samples were sent to the pathology and biochemistry laboratory, respectively. Blood and urine samples were sent to the microbiology laboratory (Bacteriology section) for culture to identify the bacteraemia. The samples were processed on blood agar, MacConkey agar, and chocolate agar to detect the growth of microorganisms. Midstream urine samples were collected in universal containers for urine culture, and they were processed in the microbiology lab in less than an hour. CLED medium was frequently used for bacterial growth, whereas Sabouraud's dextrose agar was utilized for fungal growth. Blood samples were also sent for HIV, HCV, and HBsAg serological testing.

Rapid chromatographic immunoassay was used to test for HBsAg to qualitatively detect the Hepatitis B Surface Antigen. HCV by Dot immunoassay for HCV antibody detection and HIV 1 & 2 by Dot immunoassay for HIV antibody detection.

The data was coded and entered into a Microsoft Excel spreadsheet. SPSS version 27 (IBM SPSS Statistics Inc., Chicago, Illinois, USA) was the Windows software used for the analysis. Calculating percentages, means, and standard deviations was all part of descriptive statistics. All clinical markers were compared quantitatively using the unpaired T-test, which compares quantitative data between two independent groups. For qualitative data, the chi-square and Fisher exact tests were employed whenever two or more groups were being compared. The significance level was established at a P value of less than 0.05.

Table 1: Percentage of various microorganisms isolated on blood culture.

On blood culture, most common pathogen isolated was E. coli i.e. 41%, 20% cultures were sterile, 8% had colonies of Proteus, 6% had Pseudomonas, while Klebsiella and Polymicrobial colonies was isolated in 7% patients. CONS was isolated in 3% patients, while staphylococci and Streptococci growth was observed in 2% each, and 2% patient’s blood culture shown growth of Enterobacter and Candida each. Table 2 shows organisms isolated on urine culture

Table 2: Percentage of various microorganisms isolated on urine culture.

Out of the total 100 patients’ urine cultures, maximum growth of E. coli was seen, i.e., 56% and 10% had growth of Proteus, while Klebsiella and Pseudomonas growth was observed in 9% and 7% of patients, respectively. 4% of patients’ urine cultures showed growth of CONS and Acinetobacter, and other organisms like Candida and Enterobacter; growth in urine culture was seen in 3% of study subjects each. 3% of patients had sterile urine culture reports, while Polymicrobial growth was seen in 2% of patients.

Table 3: Percentage of empirical antibiotics administered to the study subjects

In our study out of total 100 CKD patients, in empirical treatment, maximum patients 68 (68%) were treated with Cefo-Sulb, f/b 14 (14%) patients were treated with Meropenem, f/b 10(10%) were treated with Cephalexin f/b 2(2%) each was treated with Imipenem, Pip-Taz, Cefo-sulb with fluconazole, and Cefo-Sulb with Voriconazole to treat urosepsis till discharge. Table 4 shows the Antibiotic sensitivity of organisms administered to study subjects.

Table 4: Antimicrobial sensitivity profile of the microorganisms by Kirby-Bauer disk diffusion method.

In our study out of a total of 100 CKD patients, according to culture and sensitivity, the maximum number of patients i.e. 43 (43%) were treated with Cefo-Sulb, followed by 24 (24%) patients were treated with Meropenem, f/b 11 (11%) were treated with Pip-taz, followed by 7 (7%) patient were treated with Imipenem f/b 7 (7%) patient treated with Cephalexin, f/b 6 (6%) patient were treated with Levofloxacin, f/b 4(4%) patient each was treated with Ceftriaxone and Fluconazole to treat Urosepsis till discharge. It was also observed in our study that fungal infection with Candida was the most lethal organism causing death i.e. 66.67%, next lethal was Pseudomonas 62.5%, Enterobacter had 50% mortality and E. coli had least mortality of 19.23%, thus though being most common E. coli is least lethal whereas less common organism is more lethal. Thus, there was a statistically highly significant (p<0.05) association of organisms causing urosepsis and leading to mortality.

The present study is a retrospective observational study of a total of 100 patients conducted in the Department of Nephrology and Microbiology in a tertiary care institute. In the present study, 23% of blood cultures were sterile, and the rest blood cultures were E. coli, 38%, 8% had colonies of Proteus, 7% showed Pseudomonas, Klebsiella, and Polymicrobial colonies each. CONS was isolated in 4% of patients, while Staphylococci and Streptococci growth was observed in 2% each, and 1% of patients’ blood cultures showed growth of Enterobacter and Candida each. Degoricija V, et al. (2006) [18] also found a positive blood culture rate at admission of only 49% and found 31.2% E. coli, followed by 9.6% Pseudomonas aeruginosa. This finding was also supported by Sugimoto K, et al. (2013) [19] and Buonaiuto VA, et al. (2014) [20] showing E. coli as the commonest organism in blood cultures with 18% and 67% respectively. Thus, in all studies, E. Coli was the most common organism causing urosepsis.

Out of a total of 100 patients’ urine cultures, maximum growth of 52% of E. coli was seen, 11% had growth of Proteus, while Klebsiella and Pseudomonas growth was observed in 10% and 8% of patients, respectively. 5% of patients’ urine cultures had growth of CONS, and other organisms, Acinetobacter, Candida, and Enterobacter growth in urine culture was seen in 3% of study subjects each. 3% of patients had sterile urine culture reports, while polymicrobial growth was seen in 2% of patients. Our result was consistent with Sugimoto K, et al. (2013),[19] Dreger NM, et al. (2015),[12] also found E. coli most common organism for urosepsis. Tandogdu Z, et al. (2013) [14] also reported E. coli was 52% common, and 2nd common was Klebsiella 11%, in an Asian study of bacterial spectrum in urosepsis.

In our study out of a total of 100 CKD patients empirically maximum patients 64 (64%) were treated with Cefoperazone-Sulbactum, followed by 18 (18%) patients with meropenem, followed by 14 (14%) with cephalexin other less common antibiotics used were Imipenem, Piperacillin-Tazobactum, Cefo-Sulb with fluconazole, and Cefo-Sulb with Voriconazole to treat Urosepsis till discharge. In our study, out of a total of 100 CKD patients, according to culture and sensitivity, 40 (40%) patients were sensitive to Cefo-Sulb, followed by 27 (27%) patients who were sensitive to meropenem in treating urosepsis. Dreger NM, et al. (2015),[12] also found similar results to this study

Supportive therapy - 54 (54%) patients required IVF with Inotropic support for the management of urosepsis, 17 (17%) patients required hemodialysis, (32%) patients required ventilatory support for treatment, a similar result was found in research by Van Vught LA, et al. (2016) [21]. where a ventilator was required in 37 % of patients and inotropes in 22% of patients. 35 (35%) were referred for urological intervention for treatment of urosepsis. In the present study, 27 patients expired during the treatment in the hospital due to urosepsis. mortality was higher in the older age group, and the male population had more mortality than female patients, with a ratio of 2:1

In the study, the most common organism causing urosepsis was E. coli, i.e., 52%, and the most common empirical antibiotic given was Cefoperazone-Sulbactam (64%) and Meropenem (18%), while 40%patients were sensitive to Cefoperazone-Sulbactam and 27% of patients to Meropenem. We concluded that timely microbiological investigations, including culture sensitivity, help in identifying the true pathogen and also in administering the appropriate antibiotics as well as de-escalating them, thereby decreasing antibiotic burden and resistance.

Limitations

In this study, the associated risk factors and complications of urosepsis have not been assessed, as it was not one of the objectives at the start of the study.

Conflict of Interest: Nil Source of support: Nil

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