Five years trend of bacteriological profile and antibiogram of urinary tract infections at a rural medical college hospital in North Kerala, India: 2012-16

Introduction

Urinary tract infections (UTIs) constitute a major burden of bacterial infections world over.1 It accounts for approximately 150 million cases annually.2 Apart from being the most common cause of nosocomial infection among hospitalized patients, it is also the second most common cause of hospital visit.2 UTI are a significant cause of morbidity in elderly people, and in females of all ages.3 Of the various uropathogens, the Gram-negative bacteria such as Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter species cause most of the UTIs, and Gram-positive bacteria such as Enterococcus species and Staphylococcus species also contribute to causing UTIs.4 E.coli is the most common cause of both community acquired and hospital acquired cases.4 Inappropriate and empirical usage of wide spectrum antibiotics, immunosuppression and prolonged hospitalization are some of the major factors that elevate the chances of infection.4 Treatment becomes even more challenging in the presence of risk factors such as old age, comorbidity, and immunocompromised state.5 The antibiotic susceptibility pattern of uropathogens varies with types of organism, different environments and geographical locations. Therefore periodic evaluation of changing trends in the etiology and resistance pattern is necessary to update this information. The present study is carried out with the aim of finding out rate of UTI and distribution of urinary isolates in different age and sex groups and their antibiotic susceptibility pattern in a tertiary care centre in North Kerala, India.

Materials and Methods

A retrospective study was conducted in the Department of Clinical Microbiology, of 570-bedded multi-speciality medical college Hospital in North Kerala after clearance from the Institutional Ethics Committee (No. IEC/MES/26/2017). This study was conducted with an objective to determine the etiological bacterial pathogens of the Urinary tract infection and the antibiotic sensitivity pattern of pathogens isolated.

All the positive urine culture samples of outpatients and inpatients above the age of 18 years, who were suspected of urinary tract infection from January 2012 to December 2016, were included in the study. Samples included in the study were midstream clean catch urine, urine from a patient with an indwelling catheter and suprapubic/ cystoscopic aspiration. All samples collected were immediately transported to the Diagnostic Microbiology Department and processed within 2 hour. All urine samples were inoculated onto cysteine lactose electrolyte deficient (CLED) medium (Himedia, Mumbai, India) using a calibrated loop (volume-0.005 ml) and were incubated for 18-24 h at 37°C. Samples showing significant growth, bacteria growing >105 colony-forming units (CFU/mL) with single morphotype or up to 2 types, were considered significant and processed further for identification and susceptibility testing. Gram-positive organisms were processed, if isolated as pure growth even when the colony counts were <10⁴ CFU/mL. Susceptibility testing was done by Kirby-Bauer disk diffusion method and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.6 The quality control of the disc was tested by Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923.

The demographic details of the patients, the pathogen isolated and the antibiotic susceptibility pattern were collected. All samples were stratified by year, gender, ward and age wise (18–30, 31–45, 46–60 and >60 years). The year-wise cumulative antibacterial resistance rate was calculated for Gram-positive and Gram-negative organisms separately and analysed for change in the rate. The collected data were entered into Microsoft Excel and analysed.

Figure 1

Distribution of Uropathogens

Result

During the study period from January 2012 to December 2016, a total of 14,105 urine samples were received in our lab. Of these, 3939 (27.93%) were positive. Among the positive cultures, 32.42% were from male patients and 67.58% from female patients. In the ward wise distribution 48.84%, 41.08% and 10.08% the positive samples were from outpatients, Inpatients and high risk areas respectively. The geriatric patients above 61 years constituted 47.78% of the positive samples. The details of positive samples with regard to sex, ward and age group is given in detail in Table 1.

Of 3939 pathogens isolated, the gram negative bacteria constituted for 3572 (90.68%), Enterobactericiae spp. constituted 3171 (80.50%). Among them Escherichia coli, Klebsiella sp, Citrobacter sp, and Proteus sp accounted for 52.53%, 19.62%,7.31% and 1.04% respectively. Non fermenter Gram negative bacilli were 401(10.18%), Pseudomonas spp (295, 7.49%) and Acinetobacter spp (106, 2.69%). The gram positive bacteria constituted for 296 (7.51%), Enterococcus sp (196, 4.98%) and Staphylococcus sp accounted for 100 (2.54%). Fungus Candida sp. constituted 71 (1.80%). It is given in detail inTable 2.

Among all the isolated uropathogens in female patients the prevalence rate of Escherichia coli was 72.21%, followed by Klebsiella sp. 65.20%, Pseudomonas sp. 58.64%, Proteus sp. 58.54%, Citrobacter sp. 58.33% where as in male patients Acinetobacter sp. was isolated in 47.1% of cases followed by staphylococcus sp. 42%, Citrobacter sp. 41.67% given in Table 3.

The antimicrobial resistance spectrum assessment revealed that in Enterobactericiae isolates, there was a steady rise in resistance for 3^rd generation Cephalosporins (3GC) till the year 2014 followed by an increase in sensitivity in 2015 and 2016. Gentamycin resistance steadily declined from 2012 to 2016. Amikacin resistance was highest in 2014 except for proteus sp. which showed steady rise in resistance pattern till 2016. The beta lactam- beta lactamase inhibitor (PT) resistance has increased in Proteus sp., Klebsiella sp., Citrobacter sp., steadily. There was no resistance observed for meropenem in the first two years (2012, 2013), in all the isolates of enterobactericiae and non fermenter gram negative bacilli but later years showed emergence of resistance which gradually increased till 2016 (Table 4, Table 5).

The gram positive cocci showed increase in resistance to ampicillin and amoxyclav, but resistance pattern of ciprofloxacin was highest in 2012 and it gradually decreased by 2016. During the study period, we have not encountered any resistance to Vancomycin, Linezolid and Teicoplanin. We have observed increase in resistance to Amikacin over 5 years for Staphylococcus sp.

We observed that the Acinetobacter spp has emerged as a Multi –drug resistant pathogen, with increasing resistance to 3GC, Amikacin, Piperacillin Tazobactum and Meropenem to 97.87%, 23.40%, 38.30% and 80.85% respectively. Similar, trend was observed in Pseudomonas spp., E.coli and Klebsiella sp with increased resistance to these drugs (Table 4, Table 5).

Discussion

Continuous survey of antimicrobial resistance (AMR) plays an important role in the empiric treatment of UTI. Although AMR is rising all over the world, there is a significant difference in the resistance pattern across different geographical areas and also susceptibility of uropathogens varies with time.2, 7 It is therefore important to keep a continuous record of the rates of AMR in the clinically important pathogens at various regions across the world.

The present study reports a prevalence rate of 27.9 % among the patients suspected of having UTIs. Similar prevalence rates have been reported by Indian authors 22.78%8 and 32%.9 However a study from Cameroon in 2016,10 the positivity rate was 59.8%.

The study revealed that females (67.58%) were more susceptible to UTI than males (32.42%), which is similar to other studies.9, 11 Females are more prone to develop UTI, due to the characteristic anatomy of the urethra and the effect of normal physiological changes that affect the urinary tract like short urethra, its proximity to the anus, and dilation of the urethra and stasis of urine during pregnancy.9 In this study maximum numbers of isolates were from aged people i.e. above 61 years (47.8%). This result is in comprehension with other studies,12, 3 but unlike other studies where high prevalence was found in age group of 26 to 44 years.13 Predisposing factors for elderly persons for UTI include chronic diseases, functional abnormalities and certain medicines, and in women low estrogen levels which make urethra more susceptible to UTI. Infections due to Gram-negative organisms are commonly encountered in the clinical practice.

Escherichia coli (52.53 %) was the most common Gram-negative bacillus, followed by Klebsiella species (20%) and Pseudomonas species (7.5%) which is consistent with many other studies.14, 15 Our most common isolate E. coli was 52.53% the rate is less compared to western studies where it was 85%16 but similar to other Indian studies. 14 Enterobacteriace have several factors responsible for their attachment to the uroepithelium. These bacteria colonize the urogenital mucosa with adhesin, pili, fimbriae and P1-blood group phenotype receptor making them the most commonly isolated organisms.17

Among gram positive isolates Enterococcus sp. is the most common isolated organism (5%), followed by Staphylococcus aureus (2.54%), which is consistent with other study.11 However, studies from other parts of the country have shown different isolation rates, probably due to variation in geographical location or population.4 While the study from north India done reported a higher prevalence of gram positive isolates (21.79%).18 Non-fermenters are ubiquitous in the environment, able to survive in the hospital environment and can spread among hospitalized patients. They are emerging nosocomial pathogens especially in seriously ill patients and are responsible for causing a variety of infections. We have seen an upward trend in its isolation from 2012 to 2016

Antimicrobial resistance all over the world is on rise and isolates from our study were resistant to multiple drugs. Also resistance pattern varies with time which makes it difficult to start a desired treatment.4 Most of the isolates were resistant to multiple antibiotics at our setting. E.coli identified in this study were highly resistant to ampicillin < 93% and amoxyclav <85%). Studies that were conducted in India by Kothari A et al.19 showed that, the isolates of E.coli showed high resistance towards Ampicillin, amoxycilav which is in agreement with our study. Enterobactericiae family also offered around 75% resistance towards 3 GC and fluroquinolones while comparitvely less resistance to amikacin and gentamycin 13% and 40%. Resistance to fluroquinolones showed a downward trend in last five years. Similar study from central Kerala also documented a decreasing trend over years.20 In the present study, Amikacin and nitrofurantoin was found to be more sensitive among E.coli. This is similar to other study.12 There was no resistance to carbepenem in the first two years which slowly increased and in 2016 it was 46%. Multiple mechanisms like production of beta-lactamases, blocking the entry of these antibiotics, or by efflux pumps which actively pump out these antibiotics, have led to rise in the resistance against carbapenems.21 Carbapenems are often used as the last line of defense against resistant Gram-negative infections and resistance to it could result in higher cost, increased morbidity, mortality and prolonged hospitalization.

The rate of resistance to carbapenem among Gram-negative bacilli seen in our institution could possibly be due to the fact that this is a reference center, and that many of the patients had prior contact with other healthcare institutions and history of antibiotic use.

The limitations of the study were that it was a single centric, retrospective laboratory based and limited to the cases for which cultures were requested from the clinic. Information on antibiotics administered prior to culture or data on subsequent treatment and its outcome in this study population would have added meaningful data to allow a better understanding of the prevalent practice in diagnosis and treatment of UTI.

Conclusion

This retrospective study provided information on the common uropathogens and their drug resistance pattern. In this study, high prevalence of UTI was found in female gender and in geriatric patients. E. coli (53%) was the most common pathogen causing UTI. The uropathogens showed high levels of resistance to multiple urinary antimicrobial agents leading to limited option of treatment. Empirical Antimicrobials like ampicillin and amoxicillin have developed resistance to such a level that, prescribing them would definitely lead to treatment failure. In order to prevent development of resistance, antibiotic susceptibility patterns must be continuously and periodically evaluated to select the appropriate regimen to treat UTI and to avoid complications. Institutional Antibiotic policy can be tailored to achieve superior therapeutic outcome.

Source of Funding

None.

Conflict of Interest

None.