Trends in Antimicrobial Resistance in Commonly Isolated Uropathogens in a Tertiary Care Hospital Before and During Covid-19

Introduction

Urinary tract infection (UTI) is one of the common infectious presentations within community practice. About 150 million people are diagnosed with UTI each year worldwide, costing the global economy above 6 billion US dollars.¹ UTI involves either the lower urinary tract or both the upper and lower tract infections. Dysuria, frequency of urination, the urgency of urination, and occasionally suprapubic tenderness are the common characteristic features of cystitis commonly described as lower UTI.²

Beta-lactam antibiotics are the safest and most frequently prescribed antimicrobial agents for UTIs.³ They are a class of broad-spectrum antibiotics that contain a beta-lactam ring in their molecular structure. Different broad-spectrum antibiotics are often used to treat UTIs when one narrow-spectrum antibiotic could be used. This is because of the concerns about infection with resistant organisms.^4,5 Fluoroquinolones are preferred by clinicians as initial agents for empiric therapy of UTI in the area where resistance is likely to be of concern.^6,7 They have high clinical and bacteriological cure rates with lower rates of resistance amongst the most prevalent uropathogens. The protracted uses of antimicrobial agents have invariably resulted in the development of antibiotic resistance, which, in recent years has become a major problem globally.⁸

Antimicrobial resistance of uropathogens is a growing problem that complicates an effective treatment for UTI. Insights on the antimicrobial resistance patterns of pathogens causing UTIs are mandatory. The efficient and timely management of UTIs with appropriate antibiotic administration is of utmost importance to lower the risk of long-term consequences in patients. Gram-negative enteric bacilli, particularly Escherichia coli and Klebsiella spp. are the leading pathogens but in recent years Enterococcus and Staphylococcus aureus are also emerging as prominent agents. ⁹

Awareness of local antimicrobial resistance patterns is essential for evidence-based empirical antibiotic prescribing to provide appropriate treatment to the patient. An expeditious and precise diagnosis of UTI is very important to shorten the course of illness and to prevent disease progression towards the upper urinary tract and renal impairment.¹⁰ Therefore, the present study determined the antimicrobial susceptibility spectrum of commonly isolated gram-negative bacteria from patients with UTI before and during Coronavirus disease 2019 (COVID-19)to provide valuable data regardingthe recent trends of antimicrobial resistance.

Materials and Methods

This was a retrospective observational study conducted in the Department of Microbiology of a tertiary care hospital in Bengaluru. The study was carried out from January 2019 (pre-COVID-19) to June 2021 (during COVID-19). The study included patients with proven UTIs by positive growth of microorganisms in the urine sample. A positive culture was defined as the isolation of ≥ 105 colony-forming units/mL in a freshly voided midstream urine specimen. All the isolates from the culture were identified and antibiotic susceptibility was determined by VITEK 2 automated system. Antibiogram of 500 urine culture samples obtained from patients admitted to the wards were analyzed.

Statistical Analysis

The results were expressed as percentages for analyzing the distribution of different bacterial isolates and their antibiotic resistance pattern. Microsoft Excel was used for the computation of the results.

Results

Of the total 500 isolates, 200 were from the year 2019, 200 from 2020, and 100 from 2021(Figure 1). Females predominated males with a ratio of almost 3:1. In 2019, the most common pathogens isolated were E. coli (60.5%), K. pneumoniae (17%), and Acinetobacter baumannii (9.5%). In 2020, the most common pathogens isolated were E. coli (65.5%), K. pneumoniae (20%), and Pseudomonas aeruginosa (3.5%). In the first half of 2021, the most common pathogens isolated were E. coli (74%) followed by K. pneumoniae (11 %), and A. baumannii (4.5%). The most common gram-negative uropathogens during the pre-COVID-19 and COVID-19 remained the same.

The antimicrobial resistance pattern evaluated for E. coli showed increased resistance to ciprofloxacin, ceftriaxone, and cotrimoxazole whereas K. pneumoniae showed increased resistance to ciprofloxacin, ceftriaxone, and amoxicillin-clavulanic acid during the pre-COVID-19 and COVID-19.

In the year 2019, during the pre-COVID-19 period, K. pneumoniae showed increased resistance to amoxicillinclavulanic acid (97%), followed by resistance to ciprofloxacin and ceftriaxone (78%)(Figure 2).

In the year 2020, during COVID-19, K. pneumoniae showed increased resistance to ceftriaxone (62 %), followed by resistance to amoxicillin-clavulanic acid (54%), and ciprofloxacin (51%)(Figure 3).

In the year 2019, during the pre-COVID-19 period, E.coli showed increased resistance to ceftriaxone (82 %), followed by resistance to amoxicillin-clavulanic acid (79%), and ciprofloxacin (72%)(Figure 4).

In the year 2020, during the COVID-19, E. coli showed increased resistance to ceftriaxone (81 %), followed by resistance to ciprofloxacin (79 %), cotrimoxazole (62%), amoxicillin-clavulanic acid (55%)(Figure 5).

During the COVID-19 pandemic in 2021, E. coli showed increased resistance to ceftriaxone (73%), followed by resistance to ciprofloxacin (66 %), and cotrimoxazole (51 %) (Figure 6).

In the presented study, E. coli was found to be the most common pathogen associated with UTI followed by K. pneumoniae. Overall E. coli and K. pneumoniae showed higher resistance to ciprofloxacin and ceftriaxone (Figure 7).

Discussion

In recent years, uropathogens are showing a rising trend in the antimicrobial resistance pattern worldwide. The injudicious use of antimicrobial agents has paved the way for the rise of resistant pathogens to several antimicrobial agents. The easy availability of over-the-counter drugs has also contributed to the increased resistant strains. This is the main concern in developing countries where patients are not able to afford physician consultation and laboratory analysis.

In the presented study, E. coli was found to be the most common pathogen associated with UTI followed by K. pneumoniae. Overall E. coli and K. pneumoniae showed higher resistance to ciprofloxacin and ceftriaxone. Our results are in congruence with previously published studies. In a study conducted by Akram et al. in north India, 100 of the 920 samples tested showed pathogen growth, with E. coli (61%) being the most prevalent, followed by Klebsiella spp. (22%).8

A retrospective analysis of the data collected over a scattered period of 5 years revealed that E. coli was the predominant pathogen and was significantly more prevalent in girls than in boys. It was also noted that there is an increase in the resistance for cotrimoxazole from 35.58% in 2009 to 63.39% in 2014.9 In our study, it was noted that the resistance pattern of E. coli to co-trimoxazole was increased from 50% in 2019 to 62% in the year 2020.

In a previous study by Majumder et al., the frequently isolated gram negatives were E. coli (62% in 2021, 86% in 2016, and 76% in 2011) and Klebsiella spp. (11% in 2021, 10% in 2016, and 11% in 2011). The commonly isolated microbes showed a high resistance ranging from 66.67% to 93.75% towards cotrimoxazole, ciprofloxacin, cefuroxime, cephradine, amoxicillin, and nalidixic acid. Moderate resistance to ceftriaxone (64.52%) and gentamicin (53.13%) and low resistance to nitrofurantoin (25.38%) was observed.¹¹

In the study conducted by Kashyap et al., a total of 1650 urine samples from suspected UTIs were analyzed retrospectively for the isolation and identification of bacteria and antimicrobial susceptibility testing. E. coli (n = 46, 17%) was the most commonly isolated microorganism, followed by Staphylococcus spp. (n = 45, 16%). Isolated resistance to uropathogens was common with cotrimoxazole (60%), nitrofurantoin (50%), ciprofloxacin (50%), tetracycline (45%), imipenem, and cefotaxime (35%).¹²

Gunduz and Uludag et al. conducted a study in which the most common pathogen isolated was E. coli (64.2% of cases) followed by K. pneumoniae (14.9%). The overall resistance to ampicillin (62.6%), cephalothin (44.2%), co-trimoxazole (29.8%), and cefuroxime (28.7%) was significant.¹⁰

In the current study, the emerging trends in antimicrobial resistance patterns of commonly isolated urinary pathogens were analyzed and it was noted that E. coli and K. pneumoniae had an overall resistance to ciprofloxacin and ceftriaxone. The rise in the resistance to cotrimoxazole by E. coli strains was also of significance. This study provided key data to compare and monitor the current trends of antimicrobial resistance among uropathogens to enhance efficient empirical treatment.

Conclusion

E. coli is considered the most common pathogen of UTI in our center followed by K. pneumoniae. Overall E. coli and K. pneumoniae showed high resistance to ciprofloxacin and ceftriaxone with rising trends of resistance of E. coli to cotrimoxazole. Empirical antibiotic selection should be done based on the local prevalence of pathogens and their antibiotic resist ance patterns rather than on the universal guidelines. Insufficient patient adherence, inadequate treatment regimens, over-the-counter drug availability as well as antibiotic scarcity can all contribute to antibiotic resistance. The frequency of UTIs should be reduced, and the resistance pattern of bacterial pathogens to routinely used antibacterial drugs should be checked constantly. Surveillance of the antimicrobial resistance status of routinely isolated organisms is necessary to battle the ongoing crisis.

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