Introduction
Diabetes mellitus (DM) is a chronic metabolic endocrine disorder which leads to several acute and chronic complications [1], especially infection of urinary tract, respiratory tract, and soft tissues [2–5]. Urinary tract is the easily accessible for infections due to the presence of high amount of glucose in urine, which serves as a medium for pathogenic microorganisms. Further, DM is known to predispose urinary tract to bacterial infection [6]. Further, the presence of asymptomatic bacteriuria (ASB) in patients with Type 2 diabetes is considered as a predictor for subsequent urinary tract infection (UTI) in later stages [7]. Development of asymptomatic UTI in diabetic women has been reported to be three or four times more common in diabetic than in non-diabetic women or men [8–13]. The prevalence of ASB has been reported to be as high as 30% in diabetic women [14].
Female urinary tract undergoes several changes during pregnancy, which increase the risk of urinary tract infection. Following the development of ASB, several complications can develop such as UTI, pyelonephritis, pre-eclampsia, anaemia, low birth weight of foetus, retarded intrauterine growth, preterm labour, premature rupture of membrane and post-partum endometritis [15,16]. In developed countries, the awareness of ASB has led to screening and treatment of ASB during early pregnancy [17], but similar awareness is lacking in developing countries despite the widespread prevalence in Indian subcontinent [18–20]. Further, the prevalence of ASB in diabetic pregnant women was hitherto not addressed.
Aim
Hence, this study is taken up to assess the prevalence of ASB in diabetic pregnant women attending antenatal out-patient department of government tertiary hospital.
Materials and Methods
Outpatient recruitment
This study was conducted during January 2013 to December 2014 on diabetic pregnant women attending antenatal OPD at government tertiary hospital, who were willing to participate in the study. Ethical committee clearance was obtained prior to the start of the study.
Pregnant diabetic and non-diabetic women in their first, second and third trimesters without a history of urinary tract infection were included. Detailed history was obtained from each patient using a pre-designed proforma. Patients with fever or genitourinary complaints such as dysuria, urinary hesitancy, urgency, frequency, incontinence, incomplete voiding, flank/supra-pubic/hypogastric pain and patients on antibiotics were excluded from the study. After considering the history and inclusion criteria, a total of 103 pregnant diabetic women and 208 pregnant non-diabetic women were included in the study. Initially, urine sample was collected from all the participants. However, after culturing the urine, during subsequent check-ups, a second urine sample was collected only from patients with significant bacteriuria (105 organisms /mL of urine).
Collection of samples
A clean voided mid-stream urine specimen was collected into sterile specimen bottles and labelled with patient details. Initial Gram’s staining and motility tests were done. The samples were processed without delay on to Cysteine Lactose Electrolyte Deficient (CLED) medium and blood agar for semi-quantitative analysis. Patients were advised to undergo follow up after one week time. During follow up, a second urine sample was collected from women diagnosed with significant bacteriuria (>105 organisms /mL). Samples were not obtained from patients without significant bacteriuria during follow up.
Culturing of urine samples
A quantity of 0.01 mL of urine sample was inoculated on to CLED agar and Blood agar plates for semi-quantitative cultures using standard loop. The plates were incubated at 37oC overnight in an incubator. Bacterial counts were performed in a colony counter. Bacterial counts of more than 105 organisms /mL were considered as significant bacteriuria. Lower bacterial counts were considered insignificant and growth of more than two types of organisms was considered as contamination.
Antimicrobial susceptibility testing
Antimicrobial susceptibility testing was done for the isolates using Kirby-Bauer method (disc diffusion). Three to four similar colonies were selected and transferred to five mL of Mueller-Hinton broth and incubated at 37o C for 4 hours. The broth was diluted to match the optical turbidity of 0.5 McFarland standard. Using a sterile swab, the broth was streaked on the surface of Mueller-Hinton (MH) agar. The inoculum was allowed to dry for 5-15 min and antibiotic discs were placed (6 discs per plate) on the surface [Table/Fig-1]. The plates were incubated at 37oC overnight. The zone of inhibition for the respective antibiotics was recorded using Vernier callipers.
List of antimicrobial used for sensitivity testing.
| Ingredient | Quantity (μg/disc) |
|---|
| 1) Ampicillin (AMP) | 10 |
| 2) Gentamicin (GEN) | 10 |
| 3) Cephalexin (CN) | 30 |
| 4) Ceftriaxone (CTR) | 30 |
| 5) Ofloxacin (OF) | 5 |
| 6) Norfloxacin (NX) | 10 |
| 7) Cotrimoxazole (COT) | 1.25 / 23.75 |
| 8) Nitrofurantoin (NIT) | 300 |
| 9) Vancomycin (VA) | 30 |
| 10) Linezolid (LZ) | 30 |
| 11) Amoxycillin/Clavulanic acid (AMC) | 20 / 10 |
| 12) Cefoperazone/Sulbactam (CFS) | 75 / 10 |
Results
The prevalence of ASB in diabetic pregnancy was 38.83% (40/103; 95% CI: 23.73 - 53.94) and in non-diabetic pregnancy was 37.98% (79/208; CI: 27.28- 48.68). The odds ratio was 1.0225 (95% CI: 0.65 – 1.599; p=0.922) indicating that the odds of acquiring ASB was not significantly different in diabetic pregnancy compared to non-diabetic pregnancy. A chi-square test of independence showed no significant (p<0.05) difference in the prevalence of asymptomatic bacteriuria between the two groups (X2=0.021; DF=1; Sig=0.884). Further, there was no significant (p<0.05) difference in the prevalence of ASB between different age groups in diabetic pregnancy and non-diabetic pregnancy and between the groups [Table/Fig-2]. Similarly, there was no significant (p<0.05) difference in the prevalence of ASB between different periods of gestation in diabetic pregnancy and non-diabetic pregnant women and between the groups [Table/Fig-3]. Majority of the patients in diabetic pregnancy (88.35%; 91/103) and non-diabetic pregnancy (91.35%; 190/208) were from rural back ground and belonged to lower and middle class.
Prevalence of asymptomatic bacteriuria in different age groups.
| Age group | Diabetic Pregnant women | Non-Diabetic Pregnant women | Significance (p) |
|---|
| 18-22 years | 37.50 (18/48){15.13-59.87} | 40.63(26/64){21.75-59.50} | 0.990 |
| 23- 27 years | 52.00(13/25){24.84-79.16} | 38.10(32/84){21.27-54.92} | 0.673 |
| 28-32 years | 30.00(09/30){0.06-59.94} | 35.00(21/60){14.60-55.40} | 0.973 |
| Sig | 0.723 | 0.994 | |
Values in ( ) are actual numbers and in { } are 95% Confidence Intervals; Chi-square test for between and within group values using SPSS software 19.0 V (P<0.05)
Prevalence of asymptomatic bacteriuria in different periods of gestation.
| Period of gestation | Diabetic Pregnancy | Non-Diabetic Pregnancy | Sig |
|---|
| First trimester | 47.92(23/48){27.50-68.33} | 30.61(30/98){14.12-47.10} | 0.243 |
| Second Month | 27.78(05/18){-11.48-67.04} | 37.50(18/48){15.13-59.87} | 0.908 |
| Third Trimester | 32.43(12/37){5.95-58.92} | 50.00(31/62){32.40-67.60} | 0.405 |
| Sig | 0.664 | 0.299 | |
Values in ( ) are actual numbers and in { } are 95% Confidence Intervals; Chi-square test for between and within group values using SPSS software 19.0 V (P<0.05)
In diabetic pregnant women, Escherichia coli (25.00%), Staphylococcus aureus (22.50%), Coagulase negative staphylococci (20.00%), and Klebsiella pneumonia (20.00%) were the major contributors for ASB. In non-diabetic pregnant women, Coagulase negative staphylococci (32.00%), Escherichia coli (24.00%), Klebsiella pneumonia (16.50%) and Staphylococcus aureus (10.00%) were involved in ASB. The percent of isolates for each organism showed no significant (p<0.05) difference between diabetic and non-diabetic pregnant ASB [Table/Fig-4].
Type of isolates from urine samples from diabetic and non-diabetic pregnancy.
| Organism | Diabetic pregnancy | Non-diabetic pregnancy | Sig |
|---|
| Coagulase negative Staphylococci | 20.00(8/40) | 31.65(25/79)b | 0.615 |
| Escherichia coli | 25.00(10/40) | 24.05(19/79)b | 0.998 |
| Enterobacteraerogenes | 2.50(1/40) | 5.06(4/79)a | 0.933 |
| Klebsiella oxytoca | 7.50(3/40) | 7.59(6/79)a | 0.999 |
| Klebsiella pneumonia | 20.00(8/40) | 16.46(13/79)ab | 0.972 |
| Pseudomonas aeruginosa | 2.50(1/40) | 5.06(4/79)a | 0.933 |
| Staphylococcus aureus | 22.50(9/40) | 10.13(8/79)a | 0.344 |
| Chi-square test Sig. | 0.179 | 0.001 | 0.001 |
Values in parenthesis are actual numbers; Chi-square test for between group and within group values using SPSS software 19.0 V; Alphabets indicate significant difference between isolates within each group (p<0.05)
The isolates from diabetic pregnant urine samples showed highest susceptibility to nitrofurantoin (56.4%), gentamicin (38.5%), followed by cotrimoxazole (38.5%), norfloxacin (33.3%). The isolates from non-diabetic pregnant urine samples showed highest susceptibility to gentamicin (43.0%), azithromycin (32.9%) followed by norfloxacin (30.4%) and nitrofurantoin (25.3) [Table/Fig-5,6].
Susceptibility of isolates obtained from diabetic pregnant urine samples.
| Organism | CONS | E.coli | Enterobacter | K.oxytoca | K.pneumonia | P.aureginosa | S.aureus | Total |
|---|
| LZ | 5(62.5) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 4(44.4) | 9(23.1) |
| NX | 1(12.5) | 8(80.0) | 0(0.0) | 0(0.0) | 2(25.0) | 0(0.0) | 2(22.2) | 13(33.3) |
| COT | 1(12.5) | 5(50.0) | 1(100.0) | 0(0.0) | 3(37.5) | 1(100.0) | 4(44.4) | 15(38.5) |
| NIT | 1(12.5) | 9(90.0) | 1(100.0) | 1(33.3) | 3(37.5) | 1(100.0) | 6(66.7) | 22(56.4) |
| GEN | 3(37.5) | 6(60.0) | 0(0.0) | 1(33.3) | 5(62.5) | 0(0.0) | 0(0.0) | 15(38.5) |
| CN | 3(37.5) | 3(30.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 6(15.4) |
| OF | 2(25) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 2(5.1) |
| VA | 2(25) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 2(22.2) | 4(10.3) |
| AZM | 0(0.0) | 3(30.0) | 0(0.0) | 0(0.0) | 6(75.0) | 0(0.0) | 0(0.0) | 9(23.1) |
| CTR | 0(0.0) | 3(30.0) | 1(100.0) | 0(0.0) | 0(0.0) | 1(100.0) | 4(44.4) | 9(23.1) |
| AK | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) |
| AMC | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 2(25.0) | 0(0.0) | 2(22.2) | 4(10.3) |
| CFS | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 3(37.5) | 0(0.0) | 0(0.0) | 3(7.7) |
| No. of isolates | 8 | 10 | 1 | 3 | 8 | 1 | 9 | 39 |
Values in parenthesis are percentages; CONS: Coagulase negative staphylococci; AMP:Ampicillin; GEN: Gentamicin; CN: Cephalexin; CTR: Ceftriaxone; OF: Ofloxacin; NX: Norfloxacin; COT: Cotrimoxazole; NIT: Nitrofurantoin; VA: Vancomycin; LZ: Linezolid; AMC: Amoxycillin/Clavulanic acid; CFS: Cefoperazone/Sulbactam.
Susceptibility of isolates obtained from non-diabetic pregnant urine samples.
| Organism | CONS | E.coli | Enterobacter | K.oxytoca | K.pneumonia | P.aureginosa | S.aureus | Total |
|---|
| IZ | 10(40.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 4(50.0) | 14(17.7) |
| NX | 4(16.0) | 6(31.6) | 2(50.0) | 2(33.3) | 6(46.2) | 0(0.0) | 4(50.0) | 24(30.4) |
| COT | 0(0.0) | 2(10.5) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 4(50.0) | 6(7.6) |
| NIT | 0(0.0) | 12(63.2) | 0(0.0) | 2(33.3) | 4(30.8) | 0(0.0) | 2(25.0) | 20(25.3) |
| GEN | 6(24.0) | 14(73.7) | 2(50.0) | 4(66.6) | 8(61.5) | 0(0.0) | 0(0.0) | 34(43.0) |
| CN | 4(16.0) | 2(10.5) | 0(0.0) | 0(0.0) | 0(0.0) | 2(50.0) | 2(25.0) | 10(12.7) |
| OF | 10(40.0) | 2(10.5) | 0(0.0) | 2(33.3) | 0(0.0) | 0(0.0) | 2(25.0) | 16(20.3) |
| VA | 4(16.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 2(25.0) | 6(7.6) |
| AZM | 8(32.0) | 4(21.0) | 4(50.0) | 2(33.3) | 6(46.2) | 0(0.0) | 2(25.0) | 26(32.9) |
| CTR | 0(0.0) | 2(10.5) | 0(0.0) | 2(33.3) | 2(15.4) | 0(0.0) | 0(0.0) | 6(7.6) |
| AK | 0(0.0) | 2(10.5) | 0(0.0) | 2(33.3) | 0(0.0) | 0(0.0) | 0(0.0) | 4(5.1) |
| AMC | 4(16.0) | 2(10.5) | 0(0.0) | 0(0.0) | 2(15.4) | 0(0.0) | 2(25.0) | 10(12.7) |
| CFS | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) | 0(0.0) |
| No. of isolates | 25 | 19 | 4 | 6 | 13 | 4 | 8 | 79 |
Values in parenthesis are percentages; CONS: Coagulase negative staphylococci; AMP:Ampicillin; PI: Piperacillin; GEN: Gentamicin; CN: Cephalexin; CTR: Ceftriaxone; OF: Ofloxacin; NX: Norfloxacin; COT: Cotrimoxazole; NIT: Nitrofurantoin; VA: Vancomycin; LZ: Linezolid; AMC: Amoxycillin/Clavulanic acid; CFS: Cefoperazone/Sulbactam.
Discussion
Asymptomatic bacteriuria (ASB) in pregnancy is defined as the presence of more than 105 organisms per millilitre (mL) of urine taken from a clean catch mid-stream urine specimen with no symptoms referable to the genito-urinary tract [21,22]. Normally, urine is not conducive for the growth of bacteria due to acidic pH and high osmolality and urea content. The chances of occurrence of infection are further reduced due to free antegrade flow of urine in urinary tract. But in pregnancy, profound physiological and anatomical changes in urinary tract enhance the chances of infection [23–25]. Hence, the chances of ASB are much more common during pregnancy than normal condition. If untreated, ASB can progress to actual infection leading to adverse maternal and foetal outcomes [21,26].
Several factors occurring during pregnancy contribute to the development of bacterial infections during pregnancy. Enlarging uterus compresses ureter leading to hydro uterus and hydro nephrosis. Similarly, progesterone causes relaxation of smooth muscles in urinary tract leading to reduced peristalsis of ureter, relaxation of urinary bladder and retention of urine [27,28]. Decreased maternal immunity also contributes to the colonization of commensal and pathogenic bacteria in urinary tract [29]. In such cases, ASB is very likely to occurs leading to adverse maternal and foetal effects such as UTI in 30 to 40% women [30] and premature birth, low birth weight, intrauterine growth restriction and perinatal mortality in foetus [31,32]. If asymptomatic bacteriuria is left untreated 30% of mothers develop acute pyelonephritis compared with 1.8% of non-bacteriuric controls [33].
In developing countries like India, the prevalence of ASB is considered widespread [16–20]. In this study, the prevalence of asymptomatic bacteriuria during pregnancy ranged from 38.83% in non-diabetic pregnant women to 37.98% in diabetic pregnant women. Earlier, ASB was reported to account for about 2 to 10% pregnancies in developed countries [34] and up to 86.6% in developing and under-developed countries [35]. Earlier studies have reported the prevalence of ASB to be 4.00% to 23.90% during pregnancy [18,22,36]. The prevalence of ASB in this study was higher as majority of the patients included in the study belonged to middle and lower classes. The association of socio-economic status and rural background were reported to be associated with higher prevalence of ASB due to poor sanitation, lack of general hygienic and failure to attend ante-natal clinic [34,37–39].
Earlier, the prevalence of ASB was reported to be three times higher in diabetic women than in non-diabetic women [40–43]. However, some studies reported no significant difference between diabetic and non-diabetic women [44,45]. In this study, the prevalence of ASB in diabetic pregnancy revealed no significant difference with normal pregnancy. The similarity in the prevalence of ASB between normal and diabetic pregnancy can be explained by the fact that glucosuria, which is common in diabetics also occurs in 70% of pregnant women encourages bacterial growth in urine [46,47]. Similarly, we found no significant difference in the prevalence of age and period of gestation on ASB. However, previously, factors such as diabetes and anatomical abnormalities of the urinary tract [48], increasing maternal age, increasing period of gestation, multiparity, anaemia, gestational diabetes, past urinary tract infection, multiparity, advanced maternal age, lower education level, advanced gestational age and lower socioeconomic status [49], race, sickle cell disease, age and parity [50,51] were positively correlated with the prevalence of ASB. However, the effect of these factors on prevalence of bacteriuria is less clear and much controversy exists in literature [44,45].
In this study, a significantly (p<0.05) higher isolates of Coagulase negative Staphylococci and Escherichia coli were observed in urine samples of diabetic pregnancy. Earlier studies have observed that the major etiologic agent responsible for ASB is E. coli followed by other Gram negative organisms like Proteus and Klebsiella, Gram positive organisms like group B Streptococcus and Staphylococcus [23]. Several studies indicated that Escherichia coli is the most common pathogen associated with both symptomatic and asymptomatic bacteriuria, representing 70–80% of isolates [25,52,53] and up to 90% in one study [54]. Specific virulence determinants in uro-pathogenic strains of E. coli were reported to be associated with invasive infection and pyelonephritis in pregnancy [55]. Diabetes has been associated with increased incidence of urinary tract infections [3] with Staphylococcus aureus being the most common uropathogen isolated from both diabetics and non-diabetics with ASB [56]. However, some studies [57] found that coagulase-negative staphylococci (36.3%) were most prevalent in diabetes mellitus. Individuals with diabetes are reported to have increased carriage of Staphylococcus aureus, especially those using insulin [58,59], which increases the risk of staphylococcal bacteraemia and mortality [60]. In diabetics, ASB could lead to renal infections such as staphylococcus induced renal carbuncles, renal cortico-medullary abscesses and the rare but dangerous emphysematous pyelonephritis, associated with gas formation within the kidney [61].
Epidemiological studies support the relationship between the treatment of asymptomatic bacteriuria and prevention of pyelonephritis. Hill et al., observed that the incidence of hospitalization for acute pyelonephritis in pregnancy decreased after screening for asymptomatic bacteriuria became routine [62]. Treatment of bacteriuric pregnant women prevented pyelonephritis and avoided up to 20% of preterm deliveries [33,63]. However, clear consensus on the duration and choice of antibiotic is lacking in literature. The antibiotic chosen should be safe, efficacious and have low resistance rates. In this study, the isolates from both diabetic and non-diabetic pregnancy showed highest susceptibility to gentamicin. Common therapeutic regimens such as ampicillin plus gentamicin or a cephalosporin is advocated for ASB whereas ampicillin is less favoured due to high resistance rates [64–66]. The use of aminoglycoside such as gentamicin has the advantage of reaching high renal parenchymal concentrations but also poses the risk of ototoxicity and nephrotoxicity in the foetus because the drug crosses the placenta. However, gentamicin does not cause congenital anomalies, ototoxicity or nephrotoxicity after in utero exposure [67]. There exists immense scope to investigate the utility of novel antibacterial agents, which are reported to have enhanced activity over traditional antibiotics [68,69].
Conclusion
ASB is found more commonly in pregnant women due to hormonal and anatomical changes promoting growth of bacteria in urinary tract. Diabetes and other risk factors showed no association with increased prevalence. However, low socioeconomic status is strongly associated with ASB. The major isolates in ASB are Escherichia coli and Streptococcus species, which did not differ from diabetic to non-diabetic women. Gentamicin was equally efficient on the isolates from both groups.
Values in ( ) are actual numbers and in { } are 95% Confidence Intervals; Chi-square test for between and within group values using SPSS software 19.0 V (P<0.05)Values in ( ) are actual numbers and in { } are 95% Confidence Intervals; Chi-square test for between and within group values using SPSS software 19.0 V (P<0.05)Values in parenthesis are actual numbers; Chi-square test for between group and within group values using SPSS software 19.0 V; Alphabets indicate significant difference between isolates within each group (p<0.05)Values in parenthesis are percentages; CONS: Coagulase negative staphylococci; AMP:Ampicillin; GEN: Gentamicin; CN: Cephalexin; CTR: Ceftriaxone; OF: Ofloxacin; NX: Norfloxacin; COT: Cotrimoxazole; NIT: Nitrofurantoin; VA: Vancomycin; LZ: Linezolid; AMC: Amoxycillin/Clavulanic acid; CFS: Cefoperazone/Sulbactam.Values in parenthesis are percentages; CONS: Coagulase negative staphylococci; AMP:Ampicillin; PI: Piperacillin; GEN: Gentamicin; CN: Cephalexin; CTR: Ceftriaxone; OF: Ofloxacin; NX: Norfloxacin; COT: Cotrimoxazole; NIT: Nitrofurantoin; VA: Vancomycin; LZ: Linezolid; AMC: Amoxycillin/Clavulanic acid; CFS: Cefoperazone/Sulbactam.
[1]. Ramchandran A, Snehalatha C, Shyamala P, Vijay V, Viswanathan M, High prevalence of NIDDM and IGT in an elderly south Indian population with low rates of obesity Diabetes Care 1994 17:1190-92. [Google Scholar]
[2]. Nirmal J, Caputo GM, Weitekamp MR, Karchmer AW, Infections in patients with diabetes mellitus N Engl J Med 1999 341:1906-12. [Google Scholar]
[3]. Geerlings SE, Stolk RP, Camps MJ, Netten PM, Hoekstra JB, Bouter KP, Asymptomatic bacteriuria may be considered a complication in women with diabetes Diabetes Care 2000 23:744-49. [Google Scholar]
[4]. Barros MM, Cartagena SC, Bavestrello FL, Prevention of community-acquired pneumonia in adults Revista Chilena de Infectologia 2005 22:67-74. [Google Scholar]
[5]. Zhang WJ, Cai XY, Yang C, Zhou LN, Cai M, Lu XF, Cervical necrotizing fasciitis due to methicillin-resistant Staphylococcus aureus: A case report Int J Oral Maxillofac Surg 2010 39:830-34. [Google Scholar]
[6]. Nicolle LE, Asymptomatic bacteriuria when to screen and when to treat Infect Dis Clin N Am 2003 17:367-94. [Google Scholar]
[7]. Ooi S, Frazee LA, Gardner WG, Management of Asymptomatic bacteriuria in patients with diabetes mellitus Ann Pharmacother 2004 38:490-93. [Google Scholar]
[8]. Geerlings SE, Stolk RP, Camps MJ, Netten PM, Collet JT, Schneeberger PM, Consequences of asymptomatic bacteriuria in women with diabetes mellitus Arch Intern Med 2001 161:1421-27. [Google Scholar]
[9]. Reddy AS, Prevalence of asymptomatic bacteriuria and its antibiotic sensitivity in type-2 diabetic women along the sea coast International Journal of Research in Medical Sciences 2013 1:487-95. [Google Scholar]
[10]. Jain V, Asymptomatic bacteriuria & obstetric outcome following treatment in early versus late pregnancy in north Indian women Ind J Med Res 2013 137:753-58. [Google Scholar]
[11]. Vishwanath S, Asymptomatic Bacteriuria among Patients with Diabetes Mellitus at a Tertiary Care Center National Journal of Laboratory Medicine 2013 2:16-19. [Google Scholar]
[12]. Mnif MF, Kamoun M, Kacem FH, Bouaziz Z, Charfi N, Minf F, Complicated urinary tract infections associated with diabetes mellitus: Pathogenesis, diagnosis and management Indian J Endocrinol Metab 2013 17:442-45. [Google Scholar]
[13]. Chita T, Licker M, Sima A, Vlad A, Timar B, Sabo P, Prevalence of urinary tract infections in diabetic patients Rom J Diabetes Nutr Metab Dis 2013 20:99-105. [Google Scholar]
[14]. Balasoiu D, Van Kessel KC, van Kats-Renaud HJ, Collet TJ, Hoepelman AI, Granulocyte function in women with diabetes and asymptomatic bacteriuria Diabetes Care 1997 20:392-95. [Google Scholar]
[15]. Christensen B, Which antibiotics are appropriate for treating bacteriuria in pregnancy? J Antimicrob Chemother 2000 46(S1):29-34. [Google Scholar]
[16]. Uncu Y, Uncu G, Esmer A, Bilgel N, Should asymptomatic bacteriuria be screened in pregnancy? Clin Exp Obstet Gynecol 2002 29:281-85. [Google Scholar]
[17]. Vazquez J, Villar J, Treatments for symptomatic urinary tract infections during pregnancy Cochrane Database Syst Rev 2003 4:CD002256 [Google Scholar]
[18]. Lavanya SV, Jogalakshmi D, Asymptomatic bacteriuria in antenatal women Indian J Med Microbiol 2002 20:105-06. [Google Scholar]
[19]. Bandyopadhyay S, Thakur JS, Ray P, Kumar R, High prevalence of bacteriuria in pregnancy and its screening methods in north India J Indian Med Assoc 2005 103:259-62. [Google Scholar]
[20]. Ullah AM, Barman A, Siddique MA, Haque AKME, Prevalence of asymptomatic bacteriuria and its consequences in pregnancy in a rural community of Bangladesh Bangladesh Med Res Counc Bull 2007 33:60-64. [Google Scholar]
[21]. Delzell JE, Lefevre ML, Urinary tract infections during pregnancy American Family Physician 2000 61:713-21. [Google Scholar]
[22]. Sescon NI, Garingalao-Molina FD, Ycasiano CE, Saniel MC, Manalastas RM, Prevalence of asymptomatic bacteriuria and associated risk factors in pregnant women Philippine J Microbiol Infect Diseases 2003 32:63-69. [Google Scholar]
[23]. Abdullah AA, Al-Moslih MI, Prevalence of asymptomatic bacteriuria in pregnant women in Sharjah, United Arab Emirates East Med Health J 2005 11:1045-52. [Google Scholar]
[24]. Fatima N, Ishrat S, Frequency and risk factors of asymptomatic bacteriuria during pregnancy J Coll Physicians Surg Pak 2006 16:273-75. [Google Scholar]
[25]. Sharma P, Thapa L, Acute pyelonephritis in pregnancy: a retrospective study Aust N Z J Obstet Gynaecol 2007 47:313-15. [Google Scholar]
[26]. Nicolle LE, Screening for asymptomatic bacteriuria in pregnancy 1994 Ottawa Health, CanadaCanadian Guide on Preventive Health Care:100-106. [Google Scholar]
[27]. Patterson JE, Andriole VT, Bacterial urinary tract infections in diabetes Infect Dis Clin North Am 1997 11:735-50. [Google Scholar]
[28]. Jeyabalan A, Lain KY, Anatomic and functional changes of the upper urinary tract during pregnancy Urol Clin North Am 2007 34:1-6. [Google Scholar]
[29]. Scott JR, Whitehead ED, Naghes HM, Dan Forty, Obstetrics and Gynaecology 1990 6th edBostonMcGraw Hill:60-80. [Google Scholar]
[30]. Hamdan Z, Haliem HA, Ziad M, Ali SK, Adam I, Epidemiology of urinary tract infections and antibiotics sensitivity among pregnant women at Khartoum North Hospital Ann Clin Microbiol Antimicrob 2011 10:2 [Google Scholar]
[31]. Gomez R, Romero R, Edwin SS, David C, Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intra-amniotic infection Infect Dis Clin North Am 1997 11:135-76. [Google Scholar]
[32]. Goldenberg RL, Hauth JC, Andrews WW, Intrauterine infection and preterm delivery N Engl J Med 2000 342:1500-07. [Google Scholar]
[33]. Whalley P, Bacteriuria of pregnancy Am J Obstet Gynecol 1967 97:723-38. [Google Scholar]
[34]. Whalley PJ, Cunningham FG, Short-term versus continuous antimicrobial therapy for asymptomatic bacteriuria in pregnancy Obst Gynecol 1997 9:262-65. [Google Scholar]
[35]. Akerele P, Abhuliren F, Okonofua J, Prevalence of asymptomatic bacteriuria among pregnant women in Benin City Nigeria J Obstruct Gynaecol 2001 21:141-44. [Google Scholar]
[36]. Kriplani A, Bukshee K, Ratan A, Asymptomatic bacteriuria in pregnancy, Indian patients at A.I.I.M.S, New Delhi and treatment with single dose antimicrobial therapy The J Obstet Gynecol India 1993 43:489-91. [Google Scholar]
[37]. Maranchie JK, Capelouto CC, Loughlin KR, Urinary tract infections during pregnancy Infect Urol 1997 10:152-57. [Google Scholar]
[38]. Eminyat K, Fariba F, Bahram N, Asymptomatic bacteriuria amongpregnant women referred to outpatient clinics in Sanandaj, Iran Int Brazilian J Urol 2008 34:699-707. [Google Scholar]
[39]. Nicolle LE, Asymptomatic bacteriuria Curr Opin Infect Dise 2014 27:90-96. [Google Scholar]
[40]. Zhanel GG, Harding GK, Nicolle LE, Asymptomatic bacteriuria in patients with diabetes mellitus Reviews of Infectious Diseases 1991 13:150-54. [Google Scholar]
[41]. Schmitt JK, Fawcett CJ, Gullickson G, Asymptomatic bacteriuria and haemoglobin A1 Diabetes Care 1986 9:518-20. [Google Scholar]
[42]. Brauner A, Flodin U, Hylander B, Bacteriuria, bacterial virulence and host factors in diabetic patients Diabet Med 1993 10:550-54. [Google Scholar]
[43]. Abu-Bakare A, Oyaide SM, Asymptomatic bacteriuria in Nigerian diabetics J Trop Med Hy 1986 89:29-32. [Google Scholar]
[44]. Brauner A, Flodin U, Hylander B, Bacteriuria, bacterial virulence and host factors in diabetic patients Diabet Med 1993 10:550-54. [Google Scholar]
[45]. Bonadio M, Pulitano L, Catania B, Marchetti P, Miccoli R, Navalesi R, Urinary tract infection in women with controlled diabetes Pyelonephritis 1984 5:109-13. [Google Scholar]
[46]. Patterson TF, Andrriole VT, Bacteriuria in pregnancy Infect Dis Clin North Am 1987 1:807-22. [Google Scholar]
[47]. Lucas MJ, Cunningham FG, Urinary tract infection in pregnancy Clinical Obstet Gynaecol 1993 36:555-68. [Google Scholar]
[48]. Golan A, Wexler S, Amit A, Gordon D, David MP, Asymptomatic bacteriuria in normal and high-risk pregnancy Eur J Obstet Gynecol Reprod Biol 1989 33:101-08. [Google Scholar]
[49]. Akinloye O, Ogbolu DO, Akinloye OM, Terry Alli OA, Asymptomatic bacteriuria of pregnancy in Ibadan, Nigeria: a re-assessment Br J Biomed Sci 2006 63:109-12. [Google Scholar]
[50]. Pastore LM, Savitz DA, Thorp JM, Predictors of urinary tract infection at the first prenatal visit Epidemiology 1999 10:282-87. [Google Scholar]
[51]. Baill IC, Witter FR, Sickle trait and its association with birthweight and urinary tract infections in pregnancy Int J Gynaecol Obstet 1990 33:19-21. [Google Scholar]
[52]. Harris RE, Gilstrap LC, Cystitis during pregnancy: a distinct clinical entity Obstet Gynecol 1981 57:578-80. [Google Scholar]
[53]. Gilstrap LC, Leveno KJ, Cunningham EF, Renal infection and pregnancy outcome Am J Obstet Gynecol 1981 141:709-16. [Google Scholar]
[54]. Dixon HG, Brant HA, The significance of bacteriuria in pregnancy Lancet 1967 1:19-20. [Google Scholar]
[55]. Eisenstein BI, Jones GW, The spectrum of infections and pathogenic mechanisms of Escherichia coli Adv Intern Med 1988 33:231-52. [Google Scholar]
[56]. Omoregie R, Erebor YO, Ahonkhai I, Isibor JO, Ogefere HO, Observed changes in the prevalence of uropathogens in Benin City, Nigeria N Z J Med Lab Sci 2008 62:29-31. [Google Scholar]
[57]. Bissong MEA, Fon PN, Tabe-Besong FO, Akenji TN, Asymptomatic bacteriuria in diabetes mellitus patients in Southwest Cameroon Afr Health Sci 2013 13:661-66. [Google Scholar]
[58]. Tuazon Cu, Perez A, Kishaba T, Sheagren JN, Staphylococcus aureus among insulin injecting diabetic patients JAMA 1975 231:1272 [Google Scholar]
[59]. Leibovici L, Yehezkelli Y, Porter A, Regev A, Krauze I, Harrell D, Influence of diabetes mellitus and glycemic control on the characteristics and outcome of common infections Diabet Med 1996 13:457-63. [Google Scholar]
[60]. Cluff LE, Reynolds RC, Page DL, Breckenridge JL, Staphylococcal bacteraemia and altered host resistance Ann Int Med 1968 69:859-73. [Google Scholar]
[61]. Schaberg DS, Norwood JM, Case Study: Infections in Diabetes Mellitus Diabetes Spectrum 1968 15:137-40. [Google Scholar]
[62]. Hill JB, Sheffield JS, McIntire DD, Wendel GD, Acute pyelonephritis in pregnancy Obstet Gynecol 2005 105:18-23. [Google Scholar]
[63]. Smaill F, Vazquez JC, Antibiotics for asymptomatic bacteriuria in pregnancy Cochrane Database Syst Rev 2007 18:CD000490 [Google Scholar]
[64]. Mohammad M, Mahdy ZA, Omar J, Maan N, Jamil MA, Laboratory aspects of asymptomatic bacteriuria in pregnancy Southeast Asian J Trop Med Public Health 2002 33:575-80. [Google Scholar]
[65]. Kahlmeter G, An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project J Antimicrob Chemother 2003 51:69-76. [Google Scholar]
[66]. Blomberg B, Olsen BE, Hinderaker SG, Langeland N, Gasheka P, Jureen R, Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health Scand J Infect Dis 2005 37:262-68. [Google Scholar]
[67]. Dashe JS, Gilstrap LC, Antibiotic use in pregnancy Obstet Gynecol Clin North Am 1997 24:617-29. [Google Scholar]
[68]. Kumar TVC, Prasad TNVKV, Adilaxmamma K, Raj MA, Muralidhar Y, Prasad EP, Novel synthesis of nanosilver particles using plant active principle aloin and evaluation of their cytotoxic effect against Staphylococcus aureus Asian Pac J Trop Dis 2014 4(Suppl. 1):S92-96. [Google Scholar]
[69]. Kumar TVC, Muralidhar Y, Prasad EP, Prasad TNVKV, Raj MA, Evaluation of therapeutic potential of nanosilver particles synthesised using aloin in experimental murine mastitis model IET Nanobiotechnol 2013 7:78-82. [Google Scholar]