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|Urinary tract infection in critically ill patients with diabetes mellitus: Spectrum of uropathogens and antimicrobial susceptibility pattern
Nand Kishore1, Sagar Modi2, Sushant Khanduri3, Barnali Kakati4
1 Department of Anaesthesia and Critical Care Medicine, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
2 Department of General Medicine, Division of Endocrinology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
3 Critical Care Medicine, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
4 Microbiology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
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|Date of Submission||29-May-2020|
|Date of Decision||27-Jun-2020|
|Date of Acceptance||09-Jul-2020|
|Date of Web Publication||28-Aug-2020|
Background: Urinary tract infections (UTIs) are common and more severe among patients with diabetes mellitus (DM). UTI in DM is more likely to be caused by bacteria resistant to various antimicrobials. The present study aims to assess the spectrum of bacteria causing UTI and its antimicrobial susceptibility pattern among critically ill patients with DM. Materials and Methods: The present study included 272 patients with DM and UTI, age more than 18 years, admitted in the intensive care unit of a tertiary care hospital in the state of Uttarakhand, India. The pathogens causing UTI were isolated, identified and antimicrobial susceptibility testing was performed using automated VITEK method as described by the Clinical and Laboratory Standards Institute. Results: UTI was caused by Gram-negative bacteria of Enterobacteriaceae family in 89.7% and by Gram-positive bacteria in 10.3% of the study participants. Escherichia coli was the most common Gram-negative bacteria causing UTI followed by Klebsiella pneumoniae and Proteus spp. Enterococcus faecalis was most common Gram-positive isolate. Gram-negative bacteria were highly susceptible to colistin, fosfomycin, carbapenems, and aminoglycosides. Carbapenem resistance was observed in 16.4% of these isolates. Gram-positive bacteria were most susceptible to vancomycin, teicoplanin, linezolid, and fosfomycin. Conclusion: Gram-negative bacteria, particularly E. coli were the most common uropathogens causing UTI in critically ill patients with DM. These bacteria showed good antimicrobial susceptibility to colistin, fosfomycin, carbapenems, and aminoglycosides. Carbapenem-resistance was found in one-sixth of the Enterobacteriaceae isolates. Gram-positive bacteria caused UTI in about 10% of the study participants and were susceptible to vancomycin, teicoplanin, and linezolid.
Keywords: Aminoglycosides, antimicrobial susceptibility, carbapenem resistance, Escherichia coli, Enterobacteriaceae
|How to cite this URL:|
Kishore N, Modi S, Khanduri S, Kakati B. Urinary tract infection in critically ill patients with diabetes mellitus: Spectrum of uropathogens and antimicrobial susceptibility pattern. Bali J Anaesthesiol [Epub ahead of print] [cited 2021 Apr 22]. Available from: https://www.bjoaonline.com/preprintarticle.asp?id=293617
| Introduction|| |
Diabetes mellitus (DM) is a group of heterogeneous disorders sharing the phenotype of chronic hyperglycemia. The prevalence of DM in India is 7.3% according to the recent nationwide epidemiological study. Patients with DM are at higher risk of developing infections as well as infectious disease-related hospitalization and mortality.
Urinary tract infections (UTIs) are common and more severe among patients with DM., Increased susceptibility shown by patients with DM for UTI may be due to their impaired immunity, hyperglycemic milieu, and incomplete urinary bladder emptying resulting from diabetic cystopathy. UTI can range from asymptomatic bacteriuria to cystitis, pyelonephritis, and urosepsis. Serious UTI and its complications such as emphysematous pyelonephritis, renal and perirenal abscess, and renal papillary necrosis are also more frequent among patients with DM. About 50% of the patients with DM and UTI have renal scars.
Gram-negative bacteria of the Enterobacteriaceae family, particularly Escherichia coli are the most common uropathogens causing UTI in patients with DM., Patients with DM are also more prone to develop UTI caused by bacteria resistant to various antimicrobials such as extended-spectrum β-lactamase-positive E. coli, levofloxacin-resistant Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae.,,
Considering the fact that a significant number of patients with DM and UTI require hospitalization in the intensive care unit (ICU), it is of importance to examine the microbial etiology and antibiotic susceptibility in this group of patients. This information may help in planning the appropriate antibiotic therapy for the treatment of critically ill patients with DM and UTI as well as to formulate the antibiotic policy in the broader context.
The present study was planned to assess the etiology of bacterial UTI and antimicrobial susceptibility pattern among patients with DM, admitted in the ICU of a tertiary care hospital in the state of Uttarakhand, India.
| Materials and Methods|| |
This study was conducted during June 2019–January 2020, in the Himalayan Hospital, a tertiary care hospital in Uttarakhand, India. The study participants were patients with DM and UTI, age more than 18 years, admitted in the ICU of the hospital. The study protocol was approved by the Institutional Ethical Committee of the Swami Rama Himalayan University, Dehradun.
Patients were diagnosed as having UTI if they met the following criteria: (i) The presence of pyuria (a leukocyte count of >10/mm3 in urine collected from urinary catheter) and (ii) culture showing the presence of at least 105 colony-forming units/ml for Gram-negative bacteria and at least 104 colony-forming units/ml for Gram-positive bacteria. The exclusion criteria were as follows: (i) pregnancy, (ii) use of antimicrobial drugs in the last 14 days, (iii) patients who have been on urinary tract catheterization for the long period, and (iv) mixed bacterial growth in urine culture.
Urine cultures were performed in the Reference Microbiology Laboratory of the Institute. The pathogens were isolated, identified, and antimicrobial susceptibility testing was performed using automated VITEK method as described by the Clinical and Laboratory Standards Institute (CLSI). The bacterial isolates were considered susceptible to a particular antibiotic if their minimum inhibitory concentration (MIC) for that antibiotic was at or below the “Susceptible MIC breakpoints” based on VITEK AES knowledge base in accordance with the CLSI guidelines.
The data were recorded in Microsoft Excel 2010 Spreadsheets. Data were analyzed using the IBM SPSS statistics version 26 software (New York, United States). Continuous variables were compared using the independent samples t-test and categorical data were analyzed using the Chi-square test.
| Results|| |
The study included 272 participants with DM and UTI. There were 154 (56.6%) males and 118 (43.4%) females. The mean age of the study participants was 54.4 ± 15.60 years (range = 18–91 years). Males and females had comparable age (54.7 ± 15.45 vs. 54.0 ± 15.85 years; P = 0.703). [Table 1] shows age- and gender-wise distribution of the study participants. Majority of participants (74.3%) belonged to the age groups of 31–50 and 51–70 years.
|Table 1: Age- and gender-wise distribution of study participants (number and percentage)|
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Bacterial etiology of urinary tract infection
Among 272 patients studied, Gram-negative bacteria were responsible for UTI in 244 (89.7%) and Gram-positive bacteria in 28 (10.3%) patients. Most common Gram-negative bacteria causing UTI were E. coli, Klebsiella pneumoniae, and Proteus spp. Other less frequently isolated Gram-negative uropathogens were Pseudomonas aeruginosa, Citrobacter spp., and Acinetobacter spp [Figure 1].
|Figure 1: Bacteria causing urinary tract infection in study subjects (n = 272)|
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Among Gram-positive bacteria, Enterococcus faecalis and coagulase-negative staphylococci (CoNS) were the most common isolates. Enterococcus faecium and Staphylococcus aureus caused UTI in one patient each.
Overall, E. coli was the most common causative organism for UTI, isolated in 182 (66.9%) patients. This was followed in the frequency by K. pneumoniae responsible for UTI in 30 (11.0%) patients, Proteus spp. in 20 (7.4%) patients, and E. faecalis in 20 (7.4%) patients. These four bacteria were responsible for UTI in more than 90% of the study participants.
Antibiotic-susceptibility pattern in Gram-negative bacteria
[Table 2] depicts the percentage of isolates of Gram-negative bacteria that were sensitive to a particular antibiotic. In the present study, E. coli was the most commonly isolated etiological agent for UTI. The E. coli isolates were most susceptible to colistin (100%), followed by fosfomycin (98.9%), aminoglycosides (97.8%), carbapenems (89.6%), and nitrofurantoin (83%). Only one-third of E. coli isolates were sensitive to combinations of cephalosporins/penicillins with beta-lactamase inhibitors such as amoxycillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam. Majority of the isolates of E. coli were resistant to cephalosporins, quinolones, and co-trimoxazole.
The antibiotic susceptibility pattern of K. pneumoniae was similar to E. coli with the highest sensitivity (100%) to colistin. Although a large percentage of K. pneumoniae isolates was sensitive to fosfomycin (86.7%), carbapenems (73.3%), and aminoglycosides (73.3%), the frequency was less compared to E. coli. The Proteus spp. was most susceptible to carbapenems (100%), aminoglycosides (100%), fosfomycin (100%), and nitrofurantoin (90%). Only 65% of isolates of Proteus spp. were susceptible to colistin.
Among less frequently isolated Gram-negative bacterial pathogens, P. aeruginosa isolates showed the highest susceptibility to colistin (83.3%) followed by carbapenems (66.7%), aminoglycosides (66.7%), and fosfomycin (66.7%). None of the antibiotics was effective against all the isolates of P. aeruginosa. All five isolates of Citrobacter spp. were susceptible to piperacillin-tazobactam, cefoperazone-sulbactam, carbapenems, aminoglycosides, colistin, nitrofurantoin, and fosfomycin. Only isolate of Acinetobacter spp. was susceptible to piperacillin-tazobactam, cefoperazone-sulbactam, and fosfomycin. Majority of Gram-negative bacterial isolates were resistant to cephalosporins, quinolones, and cotrimoxazole.
Forty of 244 (16.4%) isolates of Gram-negative bacteria were carbapenem resistant. Carbapenem resistance was defined as the resistance to any one of meropenem, imipenem, or ertapenem. Among 40 carbapenem-resistant isolates, there were 18 isolates of E. coli, 8 of K. pneumoniae, 4 each of Proteus spp. and P. aeruginosa, 5 of Citrobacter spp. and 1 of Acinetobacter spp. Antimicrobial susceptibility of carbapenem-resistant Enterobacteriaceae is given in [Table 3]. Carbapenem-resistant isolates of E. coli were highly susceptible to aminoglycosides, colistin, and fosfomycin [Figure 2].
|Table 3: Antibiotic sensitivity of carbapenem-resistant Enterobacteriaceae (n=40)|
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Antibiotic susceptibility pattern in Gram-positive bacteria
[Table 4] shows the percentage of isolates of Gram-positive bacteria that are sensitive to a particular antibiotic. E. faecalis was the most commonly isolated Gram-positive bacteria. It showed highest susceptibility to vancomycin (100%), teicoplanin (100%), linezolid (90%), and fosfomycin (80%). One-third of the isolates of E. faecalis was susceptible to Nitrofurantoin. All E. faecalis isolates were resistant to cephalosporins, aminoglycosides, quinolones, erythromycin and clindamycin, and cotrimoxazole.
All CoNS isolates (100%) were susceptible to vancomycin, teicoplanin, linezolid, and fosfomycin. Two-thirds of CoNS isolates were susceptible to nitrofurantoin. Only isolate of E. faecium was sensitive to vancomycin, teicoplanin, linezolid, nitrofurantoin, and fosfomycin. Only isolate of S. aureus was susceptible to all the antibiotics in the panel.
| Discussion|| |
UTI is more common and is associated with higher risk of complications such as urosepsis, renal and perinephric abscess in patients with DM, compared to the nondiabetic patients. Several of these patients require hospitalization in (ICU). The present study examined the pattern of uropathogens causing UTI and its antimicrobial susceptibility among patients with DM, admitted in ICU of a tertiary care hospital.
The study involved 272 participants with slight male preponderance. This observation is similar to the study by Jagadeeswaran et al. However, these studies were not designed to assess the incidence of UTI; hence, this finding does not argue against the common observation of UTI being more common in females due to anatomical peculiarities of female urogenital tract., Majority of the patients in the present study belonged to the age groups of 31–50 years and 51–70 years, akin to the previous studies., This can be explained by the data from recent nation-wide epidemiological study which had found the highest prevalence of DM in the age groups of 35–65 years.
In the present study, UTI was most commonly caused by Gram-negative bacteria of Enterobacteriaceae family. Among these bacteria, E. coli was most frequent accounting for two-third of all cases of UTI. E. coli was followed in the frequency by K. Pneumoniae and Proteus spp. This observation is common to several studies.,,,, E. coli is believed to arise from gut, colonize the vagina and ascend the urethra to reach the bladder in females to cause UTI. A number of factors favor E. coli in causing UTI. These include the abilities of uropathogenic E. coli to (i) express several virulence factors, (ii) to survive in extra as well as intracellular environments of urothelium, and (iii) to modify host's innate immune responses.
Isolates of E. coli showed highest susceptibility to aminoglycosides, carbapenems, and colistin. Both gentamicin and amikacin were equally effective against E. coli. Jagadeeswaran et al., from India, Shill et al., from Bangladesh and He et al., from China also found high susceptibility of E. coli isolates for amikacin and meropenem.,, Majority of E. coli isolates were resistant to cephalosporins and quinolones. Other studies have also found significant resistance among E. coli isolates for cephalosporins and quinolones., Only about one-third of E. coli isolates were sensitive to amoxycillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam.
About 16% of Gram-negative bacteria were resistant to carbapenems. These included majority of isolates of P. aeruginosa, Citrobacter spp., and Acinetobacter spp. and a much smaller percentage of E. coli, K. pneumoniae, and Proteus spp. isolates. Most of these isolates were sensitive to aminoglycosides. Carbapenem resistance was observed in 4%–5% of E. coli isolates and 20% of K. pneumoniae isolates by Jagadeeswaran et al.
Considering widespread antimicrobial resistance, if possible, antibiotic therapy for UTI should be started according to urine culture and sensitivity report. However, if clinical condition of the patient necessitates empirical antibiotic therapy, aminoglycosides and carbapenems may constitute the antimicrobials of choice. Renal function parameters should be monitored while using aminoglycosides and dose of these antibiotics should be modified accordingly. Cephalosporins and quinolones are commonly used for the empirical treatment of UTI. Similarly, amoxycillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam are also frequently prescribed for empirical treatment of UTI, particularly in hospitalized patients. Data from the present study suggest caution while using these antimicrobials for the empirical treatment of UTI in patients with DM in critical care setting.
Gram-positive bacteria were responsible for UTI in only 10% of the cases. E. faecalis was the most common Gram-positive bacteria causing UTI, similar to the studies by Simkhada and Bonadio et al., All the isolates of E. faecalis were susceptible to vancomycin, teicoplanin, and 90% were sensitive to linezolid. The second-most frequent Gram-positive bacteria causing UTI were CoNS. CoNS showed 100% susceptibility to vancomycin, teicoplanin, and linezolid. Similar antimicrobial susceptibility pattern was observed in earlier studies.
We acknowledge the limitations of the present study. The findings from the present study may not be generalized to patient population living in far-off geographical locations. Clinical information pertaining to diabetes control, duration of diabetes, presence of comorbidities, and outcome of UTI would have been useful addition to the existing data.
| Conclusion|| |
In the present study, Gram-negative bacteria of the Enterobacteriaceae family, particularly E. coli were the most common uropathogens causing UTI in critically ill patients with DM. These bacteria showed good antimicrobial susceptibility to colistin, fosfomycin, carbapenems, and aminoglycosides. Considering the antimicrobial resistance pattern, cost and safety profile, carbapenems, and aminoglycosides may be considered for empirical treatment of UTI in critically ill patients with DM pending the urine culture and sensitivity report.
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Conflicts of interest
There are no conflicts of interest.
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Department of Anaesthesia and Critical Care Medicine, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun - 248 016, Uttarakhand
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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