Diversity of uropathogens and their resistogram in diabetic and non-diabetic patients in sub Himalayan region of Uttarakhand , India : A case control study

Background: Both symptomatic and asymptomatic urinary tract infections (UTIs) are thought to occur more frequently in diabetic patients. Local data about the antimicrobial resistance of Uropathogens should be available for proper therapeutic interventions of UTI. Objective: To evaluate the spectrum of the Uropathogens and their profi les of antimicrobial resistance on a series of diabetic and non-diabetic patients. Materials and Methods: A Case-Control study with 100 participants was conducted targeting the Diabetic and Non-diabetic population, symptomatic or asymptomatic for UTI. Antibiotic sensitivity test was done on each of the isolates and the results of the antibiogram were compared with that of control group (nondiabetic group). The statistical analysis was done by Chi-Square Test, Fisher exact test using statistical product and service solutions formerly known as Statistical Package for the Social Sciences (SPSS) 16.0 Version. Results: Most common isolate responsible for UTI was Escherichia coli followed by Klebsiella, Enterobacter, Proteus, Citrobacter, Acinetobacter and Candida. 93.3% and 86.6% of the isolates were sensitive to Amikacin and Amoxycillin-clavulanic acid respectively for Non Diabetics. Whereas isolates from diabetic group were 77.7 and 50% sensitive to Amikacin and Amoxycillin-clavulanic acid respectively. Highest resistance was seen for Cefuroxime for the isolates from both diabetic and non-diabetic group with 53.3 and 72.2% respectively. Signifi cant difference in resistance pattern was observed in Amoxycillin-clavulanic acid, cefazolin, piperacillintazobactam and ticarcillin-clavulanic acid. Conclusion: Culture of urine and susceptibility testing of isolated organisms is strongly advocated in the clinical management of impending complication in diabetic individuals.


INTRODUCTION
Urinary tract infections are the most commonly found bacterial infections, accounting for nearly seven million hospital visits and one million emergency department visits, resulting in 100,000 hospitalizations of women, the elderly and patients with spinal cord injuries, catheters, multiple sclerosis, HIV and also diabetes. [1]veral severe and less commonly encountered urinary tract infections (UTIs) are thought to occur more frequently in diabetic patients. [2]In a recent study from Europe, asymptomatic bacteriuria was more prevalent among women with diabetes (26%) than in women without diabetes (6%). [3]Diabetic patients are at a high risk of development of UTIs, so it is recommended that special attention is paid to them, especially for the management of bacterial UTIs. [4]Various risk factors such as sexual intercourse, age, duration of diabetes, poor glycemic control, and complications of diabetes are associated with UTI. [5]  immune system, altered bacterial adhesion to the uroepithelium, due to abnormality of Tammhorsfal protein, granulocyte dysfunction, the presence of diabetic cystopathy and microvascular disease in kidneys. [7]Moreover, among the diabetic patients, females (42.8%) are prone to UTI than males (34.1%) [8] along with high prevalence of asymptomatic bacteriuria. [9]Treatment of UTI cases is often started empirically and a large proportion of unrestrained antibiotic usage results in upsurge of resistance among the uropathogens in both community and health care settings. [10]The local data about the antimicrobial resistance of Uropathogens should be available for proper therapeutic interventions of UTI.For this purpose the study had been designed to evaluate the spectrum of the uropathogens and their profi les of antimicrobial resistance on a series of diabetic and non-diabetic patients.

RESULT
Fifty each urine samples of both diabetic and non-diabetic patients were screened for symptomatic and asymptomatic bacteriuria.Out of 50 diabetic patients 26 were males and 24 were females.[5].Among the fi rst line drug used for treating UTI, Amikacin and Amoxycillin-clavulanic acid was found to be most sensitive for the uropathogens isolated in our study.93.3% and 86.6% of the isolates were sensitive to Amikacin and Amoxycillin-clavulanic acid respectively for Non Diabetics.Whereas isolates from diabetic group were 77.for Cefuroxime for the isolates from both diabetic and non diabetic group with 53.3 and 72.2% respectively.Though the resistance pattern of most of the isolates from both the study group were not signifi cant (P > 0.05), except for Amoxycillin-clavulanic acid, cefazolin, piperacillintazobactam and ticarcillin-clavulanic acid which displayed signifi cant difference between resistogram of the two study groups [Table 6].

DISCUSSION
Over the years, evidences from many epidemiological studies have suggested that asymptomatic bacteriuria and UTI is a common occurrence in women with diabetes than in those without diabetes. [11]ong term cohort studies have also reported no negative outcomes attributable to asymptomatic bacteriuria, although women with asymptomatic bacteriuria do have an increased frequency of symptomatic infection. [12,13]Although uropathologic complications are common in men and women with diabetes, data to defi ne expected prevalence, incidence and risk factors as well as interventions to reduce the risk of developing complications are limited.Furthermore, the majority of data has been collected in patients with type 2 diabetes and in females; therefore data regarding these relationships in type one diabetes and in men are less available.Recent study has focused in the association of Asymptomatic bacteriuria ASB to diabetes. [12,14,15]Both symptomatic and asymptomatic urinary tract infection are reported to occur with increased frequency in women with diabetes. [16,17]In women without diabetes, ASB is relatively uncommon and increases risk of UTI but does not lead to serious sequelae [18] Diabetic women have a two to three fold higher prevalence of ASB and are at risk of developing more serious consequences. [14,15]Women with type two diabetes and ASB, have an increased risk for development of a symptomatic UTI [19] and women with type one diabetes are at increased risk for pyelonephritis and subsequent impairment of renal function.Uropathogens were isolated more in diabetics than in nondiabetic [Table 4].
The prospective cohort of present study illustrates the prevalence of ASB more among diabetic females (57.1%) than non-diabetic females (42.9%) followed by 58.8% diabetic and 41.2% non-diabetic males respectively [Table 3].This corroborate the reports of Raz and Stomm (1992) [,29] that females are more commonly affected with UTI than males [25] and with that of Geerlings, Stolk and Camp (2001) [12] that women with Diabetes mellitus DM are about 2-3 times more likely to have bacteria in their bladder than women without DM. [12,28] coli was the most commonly isolated Uropathogens in the urine of DM and non DM patients in our study.However, we found that there was a trend towards a lower proportion of UTI caused by the E. coli in DM compared with non-DM patients (45 versus 63 respectively) [Table 5].Other investigators have reported similar fi ndings.[20,39] Next to E. coli we isolated Klebsiella spp. of which isolation rate was 14% in diabetics and 13% in nondiabetics.This corroborates the fi ndings of other researchers who isolated klebsiella and Proteus in 12.7 and 6.3% respectively.[21] Geerlings et al., [22] isolated Klebsiella in 14.3%, Janifer et al., isolated Klebsiella in 13.5%.[23]   Subsequent isolated organisms were Proteus spp.and Enterobacter which constituted 9% of the infection among diabetic and 6% in nondiabetic.This fi nding is in total disagreement to the fi ndings of B pargavi et al., which isolated Proteus in 85% of diabetic patients.[24] DM is a common predisposing factor for UTI caused by fungi, particularly Candida spp.[20,22] This is because diabetes affects much system that protect against general infections and against UTI specifi cally.[26] Poor circulation in diabetes reduces the ability of macrophages and polymorph nuclear (PMN) cells to get away where they are required and even when they do, they are less able to phagocytize the offending bacteria and kill them than normal PMNs.It may also be due to bladder dysfunction caused by diabetic neuropathy which allows urine to remain in static pools for long period of time, providing luxurious ponds for bacteria to thrive in.[27] Changes in host defence mechanism, the presence of diabetic cystopathy and of microvascular disease in the kidneys may play a role in the higher incidence of UTI in diabetic patients. [32] Agppeared to play major role in prevalence of bacterial pathogens among DM as those between30 and 41 years and above age had more isolates [Table 2].This can be derived from the fact that people in this age group are more prone to diabetes and therefore their urine provides conducive condition for bacteria to thrive.[26] Although urologic complications are common and major health problems in men and women with diabetes, data to defi ne expected prevalence, incidence and risk factors as well as interventions to reduce the risk of developing these complications are limited.Intensive glycemic control delays the onset and progression of micro vascular complications of diabetes in both type one and type two diabetes.[30,31] Increasing antimicrobial resistance among bacteria is a major concern.The most important variable promoting resistance is the indiscriminate use of antimicrobial agents.Rational use of these agents requires the identifi cation of clinical situations in which antimicrobial therapy is not indicated.
Regarding antimicrobial resistance profile, we observed no significant difference (P > 0.05) between the two groups for ampicillin, cotrimoxazole, ciprofl oxacin and nitrofurantoin [Table 6].
Although the resistance pattern of the antibiotics summarized in [Table 6], exhibited significant difference for Amoxycillinclavulanic acid (P = 0.0039), cefazolin (P = 0.0170), Piperacillintazobactam(P = 0.019) and ticarcillin-clavulanic acid (P = 0.019) in diabetic and nondiabetic group.This requires special attention as most authors prefer antimicrobial agents which achieve high levels not only in the urine but also in the urinary tract tissue eg.Fluoroquinolones, Trimethoprim-sulfamethoxazole TMP-SMX, Amoxicillin-clavulanic acid. [35,36]Although some authors state that choice of antimicrobial remains the same as that of nondiabetic otherwise healthy subjects. [25,33,34,37,38]The eradication of microorganisms that cause UTI has been reported to be more diffi cult in diabetic patients than in nondiabetic patients because of an increased frequency of multidrug resistance. [40,41]The outcomes of the results become more prominent in the clinical management of impending complication in diabetic individuals.Our fi ndings strongly advocate culture of urine and susceptibility testing of isolated organisms in order to formulate antibiotic policy of the concerned clinical setup.
These data indicate that routine mechanisms must be established in communities to assess antimicrobial susceptibility of uropathogens and that standard regimen for empirical therapy must be reassessed periodically in light of changing susceptibility patterns.Additional types of studies would enhance our understanding of optimal management of uncomplicated UTIs.Antimicrobial resistance patterns will continue to change, implying that properly designed studies performed in a timely fashion will be necessary to maintain the affectivity of the existing antibiotics.These trials should include not only newly introduced agents but also extant antimicrobials, to gauge their relative importance.
The paucity of knowledge has been a barrier to develop the best strategy to combat the further complications of ASB and to decide the best therapeutic management with special emphasis on type of antimicrobial agent and optimal treatment duration.However, new research initiatives with bigger sample size are solicited to validate the outcome of the study.
7 and 50% sensitive to Amikacin and Amoxycillin-clavulanic acid respectively.Highest resistance was seen International Journal of Medicine and Public Health | Jan-Mar 2014 | Vol 4 | Issue 1

Table 1
non-diabetic males was 58.8% and 41.2% respectively followed by 57.1% diabetic and 42.9% non-diabetic females respectively [Table3].Escherichia coli was the most common isolate responsible for asymptomatic UTI in 45% of diabetic and 63% of non-diabetic patients followed by Klebsiella spp. of which isolation rate was 14% in diabetic and 13% in non-diabetic.Enterobacter and Proteus spp.constituted 9% of infection among diabetic and 6% in non-diabetic.Citrobacter was isolated only in non-diabetic group.
]In this study, all the patients were above 30 years of age.In diabetic group 6 (12%) patients were between 31 and 40 years of age and remaining were above 41 years, whereas 7 (14%) were between 31 and 40 years of age and remaining were above 41 years among nondiabetic group [Table2].Rate of asymptomatic bacteriuria among diabetic and