Uropathogens and their antimicrobial susceptibility pattern: A retrospective study in a district level hospital in Western Nepal

Introduction

Urinary tract infection (UTI) is one of the common health problems affecting people of all ages, race/ethnicity, sex, and circumcision status. It is caused mostly by bacteria, but viruses and fungi have also been implicated in rare cases.^1,2

Several studies have reported that there is an increased resistance of uropathogens to a number of common broad-spectrum antibiotics worldwide.^3-5 As the resistance patterns differ across different areas, every hospital should formulate their own anti-microbiogram for common infections, so as to guide the appropriate treatment.

The objective of this study is to find the prevalence of common uropathogens and, secondly, to identify antimicrobial sensitivity and resistance patterns to those pathogens.

Methods

Results

Urine samples from 1173 symptomatic patients were received for urine culture during the study period. Out of 1173 samples, 164 urine samples (14%) showed significant growth of at least one of the uropathogens tested in this study: E. coli, Staphylococcus aureus, Klebsiella spp., Acinetobacter spp. The most common pathogen isolated was E. coli (74%) followed by Klebsiella spp. as shown in Table 1.

E. coli was sensitive in 113 cases (95%) out of 119. Amikacin was tested in 87 isolates that showed 99% sensitivity. Other commonly used antimicrobial agents had lower sensitivity rates: gentamicin (83%), ciprofloxacin (75%), ceftriaxone (59%), cefixime (56%), cotrimoxazole (55%), cefotaxime (41%), and ampicillin (38%). The sensitivity pattern of other microbes is shown in Table 2.

Discussion

As with other infections, UTIs are managed initially with empirical antibiotics till the urine culture reports become available. In Nepal, most hospitals in rural areas do not have proper microbiology laboratories performing bacterial culture, so treatment is solely empirical in such cases. Our study showed E. coli as the most common pathogen (74%) causing UTI, followed by Klebsiella spp. (13%) and Acinetobacter spp. (10%). Similar findings have also been reported in different studies conducted in Nepal and other countries.^4-7 So, empirical antibiotics to treat UTI should target E. coli.

Among 119 samples of E. coli tested for nitrofurantoin, it was sensitive in 113 cases (95%). Amikacin was tested in 87 isolates that showed 99% sensitivity. Other commonly used antimicrobial agents had lower sensitivity rates: gentamicin (83%), ciprofloxacin (75%), ceftriaxone (59%), cefixime (56%), cotrimoxazole (55%), cefotaxime (41%), and ampicillin (38%). Various studies done in Nepal have also shown lower sensitivity of the pathogen to these agents.^3,14 Our study suggests that nitrofurantoin would be a good first-choice oral antibiotic for managing lower UTI such as cystitis. However, in pyelonephritis or prostatitis, nitrofurantoin is not recommended as it does not attain sufficient concentration in these tissues. Based on our study results, aminoglycoside amikacin (parenteral) can be used empirically for pyelonephritis, or when a patient does not tolerate oral medicine. In a prospective cohort study conducted in Singapore from 2015 to 2016, E. coli was sensitive to amikacin in 100% of the cases.⁶

Other commonly used oral antimicrobial agents like ciprofloxacin, cotrimoxazole and cefixime had lower sensitivity to E. coli. They had been used rampantly in Nepal in the past, mainly for typhoid fever. This explains the increase in resistance to these agents. Several studies done in Nepal and abroad have also shown higher resistance of E. coli to these antibiotics.^3,4,7-10 Ceftriaxone one of the most commonly used antibiotic in hospitalized patients in Nepal, however its sensitivity to E. coli was only 59%, hence its empirical use in hospitalized UTI patients should be discouraged.

Klebsellia spp. was found to be more sensitive to antimicrobrial agents as compared with E. coli. It was sensitive in all 16 samples tested for ciprofloxacin, 14 samples tested for amikacin, 17 out of 18 samples tested for cotrimoxazole (94%) and 16 out of 17 tested samples tested for gentamycin (94%). However, a study done at KIST Medical College from March 2013 to April 2014 showed that Klebsellia spp. obtained from all urine samples were multidrug resistant and extended spectrum beta lactamase producers. ¹⁵

Acinetobacter spp. was more resistant compared with other microbes isolated in this study. It was resistant in all 16 cases tested for cefotaxime, 11 out of 15 samples tested for ceftriaxone (73%), 10 out of 15 samples tested for cotrimoxazole (67%), four out of seven samples for gentamycin (36%) and three out of seven samples for amikacin (30%). Similar to this study, a study published in The Pan African Medical Journal also showed Acinetobacter spp. resistant to commonly administered antibiotics with high susceptibility to amikacin.¹⁶

Multidrug-resistant organisms are resistant to at least one agent in three or more classes of antimicrobial agents. The rising incidence of a multidrug resistance phenotype of extended-spectrum beta-lactamase (ESBL) genes and fluoroquinolones resistance, has become a global concern because of their potential cause of serious infections which are difficult to treat.¹² In this study, MDR was isolated in 52 out of 122 cases of E. coli (43%), 13 out of 16 cases of Acinetobacter spp. (81%) and five out of 21 cases of Klebsiella spp. (24%). Significant proportions of MDR uropathogens were seen in other studies too, done in different hospitals of Nepal.^5,13 Antimicrobial resistance (AMR) is a major concern in both developed and developing countries as various studies have shown its rising incidence. It has posed a major challenge for successful treatment of infectious diseases. With increased prevalence of irrational and injudicious use of antimicrobial agents and inadequate antibiotic stewardship programs, it is a major burden for Nepal.¹⁴ Even in rural areas like Beni, Myagdi, all classes of antimicrobial agents are easily available. In our experience antibiotics have been sold mostly without proper diagnostic evaluation of patients and prescription of physicians in both major cities and rural areas of Nepal.

In Beni hospital, culture and sensitivity were not routinely sent in all clinically suspicious cases of urinary tract infections. Also, sensitivity was not tested on all appropriate classes of antimicrobial agents. Had it been done, we would have a broader view of sensitivity and resistance pattern. As we are collecting more data on this matter, we will have analysis of more data in the future which would give a more accurate prospect of the antimicrobial susceptibility pattern in this hospital.

The susceptibility patterns of antimicrobial agents to microbes vary from country to country and also in different regions of the same country. The guidelines used in Western countries may not be useful in Nepal. It is necessary to identify the sensitivity pattern in a particular location and to develop the treatment protocol accordingly. Very few studies have been published regarding AMR in the Gandaki province of Nepal.¹⁴ This study will help for selection of appropriate empirical antimicrobial agents for treatment of UTI in this region.

The limitation of the study is external validity. As data were collected from a single hospital, our findings cannot be generalized and multicenter studies with larger sample size are needed to find out the real scenario of antimicrobial resistance pattern and formulation of treatment guidelines accordingly. Also patient information like genitourinary malformations, prior exposure to antibiotics, recent hospitalization or prior history of UTI were not taken into consideration, which can be important risk factors for resistant uropathogens.

Conclusions

E. coli is the most common pathogen associated with urinary tract infection in Beni hospital. It is resistant to broad-spectrum penicillin, third-generation cephalosporins and fluoroquinolones. Resistance to nitrofurantoin is low and could be the antibiotic of choice for uncomplicated cystitis. Amikacin showed promise as a suitable intravenous agent but needs further studies with adequate sample size

Data availability

Author Contributions:

Manoj Ghimire- Conceptualization, Data Curation, Formal Analysis, Supervision, Methodology, Writing – Original Draft Preparation

Sudeep Adhikari- Supervision, Writing – Original Draft Preparation, Writing – Review & Editing

Kalpana Ghimire- Data Curation, Project Administration, Supervision, Writing – Review & Editing

Bishal Tiwari- Project Administration, Supervision, Writing – Review & Editing

Soni Koju- Data Curation, Writing – Original Draft Preparation

Sajana Poudel- Conceptualization, Project Administration, Data Curation

Sulab Khanal-Data Curation, Methodology