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Volume10•Issue3•July-September2022 ISSN:2666-1802

APIK
Journal of Internal Medicine
APIK Journal of Internal Medicine ● Volume 10 ● Issue 3 ● July-September 2022 ● Pages ***-***

An Official Publication of The Association of Physicians of India,


Karnataka Chapter, Bengaluru

Chief Editor
Dr. M.Premanath www.ajim.in

AJIM
Original Article

Asymptomatic Bacteriuria – Spectrum of Organisms and


Antibiotic Resistance Pattern in Women with Type 2 Diabetes
Mellitus
B. S. Meghana, K. Ravi
Department of General Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Abstract
Background: Diabetes mellitus (DM) is a major health challenge worldwide. It is a risk factor for the development of asymptomatic bacteriuria (ASB)
and urinary tract infection. Although the current guidelines do not recommend treatment of ASB among women with type 2 diabetes, it emphasizes
the need for therapeutic trials based on culture sensitivity patterns. This study was aimed to determine the spectrum of organisms causing ASB and
antibiotic sensitivity patterns. Therefore, we believe that this study would serve as road map to conduct therapeutic trials in subjects with ASB based
on antibiotic sensitivity patterns. Methods: Cross‑sectional study was conducted including both outpatients and inpatients on 250 Women with T2DM
with no symptoms of UTI, were investigated with FBS, PPBS , HbA1C, Urine routine-microscopy and Urine culture- sensitivity. The presence
of ASB among women with T2DM was studied, and antibiotic sensitivity pattern was analyzed. Statistical Package for the Social Sciences (SPSS)
version 20 was used for statistical analysis. Results: The frequency of ASB in our study was found to be 39 out of 250 diabetic women, that is,
15.6%. The mean HbA1c was higher among diabetic women with ASB (9.63%) than without ASB (8.42%). Escherichia coli (58.97%) was the most
common organism. Antibiotic sensitivity showed that most organisms were sensitive to amikacin (64.1%), followed by nitrofurantoin (59.0%). Most
organisms were resistant to fluoroquinolone (79.5%). Conclusions: E. coli was the most common organism causing ASB in our study. Antibiotic
sensitivity showed that most organisms were resistant to fluoroquinolones and were sensitive to amikacin. Further large‑scale studies are required
to study the effect of antibiotic sensitivity‑directed therapeutic trials to conclude the efficacy of therapy in patients of ASB.

Keywords: Antibiotic sensitivity pattern, asymptomatic bacteriuria, diabetes, HbA1c, organisms isolated

Introduction causes changes in the urinary tract that make women more
vulnerable to bacteriuria.[3]
Diabetes mellitus (DM) has become a major health challenge
worldwide. In India alone, the prevalence of diabetes is expected Diagnosis of ASB is considered when a patient who
to increase from 31.7 million in 2000 to 79.4 million in 2030.[1] undergoes screening urine culture for a reason unrelated
The prevalence of asymptomatic bacteriuria (ASB) in diabetic to the genitourinary tract and is incidentally found to have
patients is four times higher than the general population. ASB bacteriuria.[4] It has been proposed that transient bacteriuria
is also a common precursor to urinary tract infections (UTIs).[2] merely reflects colonization of the bladder without tissue
ASB is defined as the presence of at least 105 colony‑forming invasion, which clears spontaneously, however, in few
units/ml in clean‑voided midstream urine sample from susceptible patients, especially with DM, it can progress to
an individual without symptoms of UTI such as dysuria, symptomatic infection with pyuria over the time.[5]
frequency, urgency, abdominal distention, or fever.[1] ASB
and UTI are more common in women due to shorter urethra Address for correspondence: Dr. B. S. Meghana,
than males. After menopause, a decline in circulating estrogen #372, Sri Vasu Nilaya, 10th Cross, Avalahalli Bda Layout, Girinagar,
Bengaluru ‑ 560 085, Karnataka, India.
Received: 15.02.2021   Reviewed: 06.01.2022
E‑mail: meghanabshivanna@gmail.com
Accepted: 08.02.2022   Published: 12.07.2022
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DOI: How to cite this article: Meghana BS, Ravi K. Asymptomatic bacteriuria
10.4103/ajim.ajim_19_21 – Spectrum of organisms and antibiotic resistance pattern in women with
type 2 diabetes mellitus. APIK J Int Med 2022;10:164-8.

164 © 2022 APIK Journal of Internal Medicine | Published by Wolters Kluwer - Medknow
Meghana and Ravi: ASB in T2DM women – resistance pattern

In general, there is little evidence that routine treatment of positive In our study, we aimed to determine the spectrum of organisms
cultures is required, except during in pregnancy, children, patients causing ASB in diabetics and antibiotic sensitivity patterns
for kidney transplantation, and elderly bedridden patients.[5,6] which could help to determine the common organisms in
the clinical picture and to select the antibiotic group for
It is suggested that in diabetic patients, glycosuria favors
prophylactic therapy in women with T2DM.
the growth of pathogenetic organisms and causes either
ASB or symptomatic UTI. ASB has higher risk of becoming
complicated UTI and is associated with reduced GFR. Methods
[7]
Emphysematous pyelonephritis, cystitis, bacteremia, Study was conducted on 250 women with T2DM (as per
perinephric abscess, and renal papillary necrosis are common WHO criteria) with no symptoms of UTI including both
in diabetics.[8] Hence, whether ASB requires treatment is still outpatients and inpatients in a tertiary health center. It is a
a question, especially in patients with DM.[2,9] cross‑sectional study. Women with T2DM with symptoms
Current guidelines – IDSA 2019 Clinical Practice Guideline for of UTI, prior bladder catheterization, surgery of urogenital
the Management of ASB does not recommend treatment of ASB tract, preexisting renal diseases, renal calculi, or who have
among women with type 2 diabetes.[5] However, guidelines states received antimicrobial drugs in the last 14 days were excluded
that there is a need for further studies to analyze the effectiveness from the study. After taking written informed consent, history
of treatment among women with type 2 DM (T2DM). was taken, and examination was performed. Women with
T2DM with no symptoms of UTI were investigated with
FBS, PPBS , HbA1C, Urine routine-microscopy and Urine
Table 1: Baseline characteristics of study population culture- sensitivity. Antibiotic sensitivity testing of the isolated
Frequency (%) strains was done by Kirby–Bauer’s disc diffusion method. The
Age (years) presence of ASB among women with T2DM was studied, and
<40 26 (10.4) antibiotic sensitivity pattern was analyzed.
40-49 52 (20.8) Statistical analysis was done by SPSS (Statistical Package for
50-59 62 (24.8)
the Social Sciences) version 20. (IBM SPSS statistics [IBM
≥60 110 (44)
corp. Armonk, NY, USA released 2011]) was used to
Duration of diabetes (years)
perform the statistical analysis. Data were entered in the
<5 96 (38.4)
Excel spreadsheet. Descriptive statistics of the explanatory
5-10 102 (40.8)
>10 52 (20.8)
and outcome variables were calculated by mean, standard
FBS (mg/dl) deviation (SD) for quantitative variables, frequency and
<80 7 (2.8) proportions for qualitative variables. Inferential statistics such
80-130 58 (23.2) as Chi‑square test were used to test the significance between
131-160 39 (15.6) qualitative variables. Unpaired t‑test was applied to test the
161-190 24 (9.6)
>190 122 (48.8)
PPBS
Table 3: Mean Fasting blood sugar, Postprandial blood
≤180 29 (11.6)
sugar, and HbA1c distribution of the study subjects with
181-250 81 (32.4) respect to asymptomatic bacteriuria
251-350 94 (37.6) Variables ASB n Mean SD Mean P
>350 46 (18.4) difference
HbA1c FBS Positive 39 238.54 82.11 43.647 0.005
≤7 87 (34.4) Negative 211 194.89 88.60
7.1-9 73 (29.2) PPBS Positive 39 296.41 83.77 23.126 0.147
9.1-11 38 (15.2) Negative 211 273.28 92.61
11.1-13 34 (13.6) HbA1C Positive 39 9.63 2.50 1.208 0.006
>13 18 (7.2) Negative 211 8.42 2.51
FBS: Fasting blood sugar, PPBS: Postprandial blood sugar FBS: Fasting blood sugar, PPBS: Postprandial blood sugar, SD: Standard
deviation, ASB: Asymptomatic bacteriuria

Table 2: Mean age distribution of the study subjects with


respect to culture Table 4: Distribution of study subjects according to urine
culture
Variables Culture N Mean SD Mean P
difference Urine culture Frequency (%)
Age Positive 39 54.51 13.37 −2.046 0.366 Negative 207 (82.8)
Negative 211 56.56 12.90 Positive 43 (17.2)
SD: Standard deviation Total 250 (100.0)

APIK Journal of Internal Medicine ¦ Volume 10 ¦ Issue 3 ¦ July-September 2022 165


Meghana and Ravi: ASB in T2DM women – resistance pattern

Table 5: Antibiotic sensitivity pattern among asymptomatic bacteriuria‑positive cases


Antibiotic sensitivity Penicillin, n (%) Cephalosporin, n (%) Fluoroquinolone, n (%) Co‑trimoxazole, n (%) Nitrofurantoin, n (%)
pattern
0 10 (25.6) 10 (25.6) 7 (17.9) 12 (30.8) 23 (59.0)
1 28 (71.8) 28 (71.8) 31 (79.5) 22 (56.4) 6 (15.4)
2 1 (2.6) ‑ ‑ ‑ 5 (12.8)
3 ‑ 1 (2.6) 1 (2.6) 5 (12.8) 5 (12.8)
Total 39 (100) 39 (100) 39 (100) 39 (100) 39 (100)
0=Sensitive, 1=Resistant, 2=Intermediate, 3=Not tested

Table 6: Antibiotic sensitivity pattern among asymptomatic bacteriuria‑positive cases


Antibiotic Piperacillin, n (%) Amikacin, n (%) Tigecycline, n (%) Colistin, n (%) Imipenem, n (%)
0 16 (41.0) 25 (64.1) 16 (41.0) 14 (35.9) 16 (41.0)
1 18 (46.2) 11 (28.2) 1 (2.6) ‑ 15 (38.5)
2 1 (2.6) ‑ ‑ ‑ 2 (5.1)
3 4 (10.3) 3 (7.7) 22 (56.4) 25 (64.1) 6 (15.4)
Total 39 (100.0) 39 (100.0) 39 (100.0) 39 (100.0) 39 (100.0)
0=Sensitive, 1=Resistant, 2=Intermediate, 3=Not tested

Urine sample of 17.2% (43 patients) was positive for


Table 7: Organisms isolated from urine culture among
organisms. On further evaluation, 15.6% (39 patients) had
women with Type 2 diabetes with asymptomatic
positive bacterial culture [Table 3].
bacteriuria
Organisms isolated Number of patients with ASB, Among women with T2DM with ASB, the mean age was
from urine n (%) 54.51 years; SD was 13.37 with P = 0.366 suggesting no
E. coli 23 (58.97) statistically significant difference between ASB‑positive and
Enterococcus 2 (5.13) negative cases. There was a significant association of ASB with
GNNF 1 (2.56) HbA1c and FBS, but PPBS was not significantly associated
E. coli and Klebsiella 1 (2.56) with ASB among women with T2DM [Table 4]. Although mean
Klebsiella 7 (17.95) FBS was higher among both the groups of women with T2DM,
P. agglomerans 1 (2.56) it was comparatively more elevated with ASB (238.54 mg/dl)
Pseudomonas 3 (7.69) than without ASB (194.89 mg/dl); similar results were seen
S. aureus 1 (2.56) with mean HbA1c was comparatively more elevated among
Total 39 (100) women with type 2 diabetes (9.63%) with ASB than without
E. coli: Escherichia coli, GNNF: Gram‑negative non fermenters, P.
agglomerans: Pantoea agglomerans, S. aureus: Staphylococcus aureus,
ASB (8.42%).
ASB: Asymptomatic bacteriuria In our study, it was found that 64.1% of ASB‑positive cases
were sensitive to amikacin, 59.0% showed sensitivity to
statistical difference between two quantitative variables. The nitrofurantoin among tested antibiotics. Resistance pattern
level of significance was set at 5%. of organisms was studied which showed that 79.5% of
ASB‑positive cases were resistant to fluoroquinolones, 71.8%
Results of ASB‑positive cases were resistant to both penicillin and
cephalosporins [Tables 5 and 6].
There were 250 participants (women with T2DM) included
in the study. Age of the patients ranged from 29 years The frequency of ASB among women with T2DM was
to 90 years with a mean of 56.2 years [Tables 1 and 2]. 15.6%. It was significantly more common among patients
Predominant group of patients had diabetes for 5–10 years. with poor glycemic control (HbA1c >7%). Escherichia
In the study population, 74% (185) of patients had coli was the most common organism isolated, followed by
elevated FBS greater than the target range as per ADA Klebsiella [Table 7].
guidelines [Table 1]. Postprandial blood sugar levels were
tested, and 88.4% (221) of patients had PPBS greater Discussion
than target range as per ADA guidelines, that is, more The prevalence of ASB is ~ 5% among women between ages
than 180 mg/dl. In our study, 65.6% (164 patients) had 20 and 40 years and may be as high as 40%–50% among
HbA1c >7% and 34.4% (86 patients) had HbA1c <7%. The elderly women and men.[1] In a study done by Dalal et al.[4]
frequency distribution of HbA1c is shown in Table 1. the prevalence of ASB varied from 9% to 27%. In a study

166 APIK Journal of Internal Medicine ¦ Volume 10 ¦ Issue 3 ¦ July-September 2022


Meghana and Ravi: ASB in T2DM women – resistance pattern

Table 8: Results from various studies done on asymptomatic bacteriuria


Study Year of Number of Patient type ASB MC HbA1c correlation
publication patients prevalence (%) organism
Adhikaree A et al.[19] 2015 116 DM 10.3 E. coli Associated with poor glycemic control
Bharti A et al.[11] 2019 100 T2DM 21 E. coli Associated with poor glycemic control
Bissong MEA et al.[20] 2013 265 Both* 33.2 CONS Not studied
Bonadio et al.[21] 2006 346 DM 12.9 E. coli Not studied
Bonadio et al.[22] 2004 228 DM women 17.5 E. coli Associated with poor glycemic control
Meiland et al.[23] 2006 644 Women 17 E. coli Associated with poor glycemic control
Mohan S et al.[24] 2017 150 DM 16 E. coli Not studied
Renko et al.[25] 2011 3579 Both* 12.2 E. coli Associated with poor glycemic control
Rijal M et al.[26] 2015 467 DM 18.42 E. coli Not studied
Venkatesan KD et al.[10] 2017 100 DM 32 E. coli Not studied
Vishwanath et al.[27] 2013 100 DM 4 E. faecalis Associated with poor glycemic control
Results of the current study 250 T2DM women 15.6 E. coli Associated with poor glycemic control
*Diabetics and nondiabetics. MC: Most common, DM: Diabetes mellitus, T2DM: Type 2 DM, E. faecalis: Enterococcus faecalis, E. coli: Escherichia coli,
ASB: Asymptomatic bacteriuria, CONS: CoNS-Coagulase-negative staphylococci

done by Venkatesan et al.[10] among 100 diabetic patients, with DKA or patients with significant immunosuppression.
the prevalence of ASB was 32%. In a similar study done by Some studies, however, have suggested the use of prophylactic
Bharti et al.[11] the prevalence of ASB was 21%. In our study, measures such as probiotics may be beneficial in avoiding UTIs
the frequency of ASB was found to be 15.6% (39 among 250 and its possible complications.[18]
women with type 2 diabetes). Although no definitive comment
Therefore, we believe that this study will be road map study for
can be made, high prevalence in few studies could be explained
future researchers who would like to conduct therapeutic trials
by different inclusion criteria.
on subjects with ASB and diabetes on the basis of antibiotic
ASB in type 2 diabetic women was noted to be an independent sensitivity patterns.
risk factor for UTIs.[12]
Financial support and sponsorship
It has been found that as the duration of diabetes increases, there Nil.
is an increased risk of both ASB and UTIs.[13] Some studies also
suggest to consider ASB as a complication of long‑standing Conflicts of interest
diabetes, along with albuminuria and peripheral neuropathy [12,14] There are no conflicts of interest.

ASB was significantly more common among patients with


poor glycemic control (HbA1c >7%) which was consistent
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168 APIK Journal of Internal Medicine ¦ Volume 10 ¦ Issue 3 ¦ July-September 2022

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