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Asian Pac J Trop Med 2014; 7(Suppl 1): S116-S120

Contents lists available at ScienceDirect

Asian Pacific Journal of Tropical Medicine journal homepage:www.elsevier.com/locate/apjtm

Document heading

doi: 10.1016/S1995-7645(14)60216-9

Antibiotic

sensitivity pattern from pregnant women with urinary tract infection in Bangalore, India Sibi G , Pinki Kumari, Kabungulundabungi Neema *

Department of Biotechnology, Indian Academy Degree College, Centre for Research and Post Graduate Studies, Bangalore, India

ARTICLE INFO

ABSTRACT

Article history: Received 23 Jun 2014 Received in revised form 10 Sep 2014 Accepted 15 Sep 2014 Available online 19 Sep 2014

Objective: To determine the antibacterial profile of pregnant women with urinaty tract infections and analyze the antibiotic sensitivity pattern for the effective treatment. Methods: A total of 395 urine samples from pregnant women with different gestational age were processed for the isolation of uropathogens and tested against eight groups of antibiotics namely penicillins, cephalosporins, fluoroquinolones, aminoglycosides, macrolides, lincosamides, glycopeptides and sulfonamides. Results: A positive culture percentage of 46.6% was obtained with the highest urinary tract infection in third trimester gestational age. Among the uropathogens isolated, 85.6% were Gram negative and 14.4% were Gram positive with Escherichia coli as the predominant bacteria (43.9%) followed by Klebsiella oxytoca (19.4%) and Klebsiella pneumoniae (13.3%). Antibiotic sensitivity assay revealed that amikacin had the highest overall sensitivity (n=136; 76.7%) and the subsequent highest sensitivity was observed with ciprofloxacin (n=132; 73.3%), clindamycin (n=124; 68.9%), cefotaxime (n=117; 65%) and nalidixic acid (n=115; 63.9%). Conclusions: The findings revealed that uropathogens were more resistant to penicillins, macrolides and glycopeptides which restrict their use in treating urinaty tract infections during pregnancy. In conclusion, common causative bacteria and their antibiotic sensitivity pattern are to be determined along with their safety to mother and fetus for the effective treatment of urinary tract infections during pregnancy.

Keywords: Urinary tract infection Pregnancy Uropathogens Amikacin

1. Introduction Urinary tract infection (UTI) in women are more prevalent due to their short urethra and its anatomical proximity to the anal orifice[1,2]. UTIs are most common bacterial infection which complicates pregnancy[3]. Pregnancy causes numerous hormonal and mechanical changes in the body. Beginning in the sixth week, with peak incidence during 22nd to 24th weeks, 90% of the pregnant females develop urethral dialatation increasing the risk of urinary stasis and vesicouretral reflux[4]. Further, glycosuria and aminoaciduria during pregnancy are additional factors to facilitate *Corresponding author: Sibi G, Department of Biotechnology, Indian Academy Degree College, Centre for Research and Post Graduate Studies, Bangalore, India. E-mail: [email protected]

bacterial growth[5]. UTIs in pregnancy left untreated leads to maternal and perinatal morbidity and mortality[6]. Untreated bacteriruia during pregnancy is associated with low birthweight and premature delivery[7]. Resistance development to previously effective antibiotics by the uropathogens has been reported globally in recent years[8,9], and their susceptibility vary from place and time[10]. There are two major challenges while treating UTI s in pregnancy; protection of fetus and resistance development of uropathogens. Physicians must consider possible side effects from drugs to protect maternal and fetal safety while prescribing antibiotics[11,12]. At the same time the chosen antibiotic should have efficacy and low resistance rates in a given population[13,14]. I solation of pathogens associated with UTI s and determining their antibiotic sensitive pattern will

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potentially reduce the inappropriate prescription of antibiotics and resistance development. Further, detection of changing susceptibility pattern by the uropathogens against commonly used antibiotics is one effective strategy for empirical treatment. This study evaluates the antibiotic susceptibility pattern of uropathogens from pregnancy. 2. Materials and methods 2.1. Study population A total of 395 urine samples from pregnant women with

or without having symptoms of UTI were collected during October 2012 to January 2014. The age of people included in the study ranged from 25-40 years. Verbal informed consent from target population and approval from institutional research ethical committee were obtained before starting the experiment. 2.2. Inclusion and exclusion criteria F emale patients aged between 25 - 40 years with uncomplicated UTI symptoms like frequency, urgency and dysuria were included in the study. Pregnant women on antibiotics within the last 2 weeks and those who could not give consent to participate in the study were excluded.

2.3. Sample collection and processing Clean catch midstream urine samples were collected

into a sterile screw capped universal container by standard method. The samples were labeled and 0.2 mg of boric acid was added to prevent the bacterial growth in urine samples. The samples were cultured on cysteine-lactose electrolyte deficient agar and blood agar using a sterile 4 mm platinum wired calibrated loop for the isolation of microorganisms. The plates were incubated for overnight at 37 °C and the samples were considered positive when an organism was cultured at a concentration of 104 CFU/mL which was estimated through multiplying the isolated colonies by 1 000. The isolates were identified up to the species level by standard biochemical tests[15]. 2.4. Antibiotic sensitivity assay A ntibiotic sensitivity testing was performed by

the modified disc diffusion method as per the recommendations[16]. Inoculums adjusted to 0.5 McFarland standard was swabbed on Mueller Hinton agar plates for antibiotic sensitivity assay. Eight groups of antimicrobials such as penicillins, cephalosporins, fluoroquinolones, aminoglycosides, macrolides, lincosamides, glycopeptides and sulfonamides were selected based on frequent prescription and used in this study. Among the group, the antibiotics tested were amoxicillin (10 µg), oxacillin (10 µg), cloxacillin (5 µg), cefotaxime (10 µg), ceftriaxone (30 µg), nalidixic acid (30 µg), ciprofloxacin (5 µg), norfloxacin (10 µg), amikacin (30 µg), gentamycin (10 µg), erythromycin (10 µg), clindamycin (2 µg), vancomycin (30 µg) and co-trimoxazole (30 µg). Statistical analysis was done using Chi-square test and student’s t-test. 3. Results Among the 395 samples collected, 180 were laboratory

confirmed cases of UTI with a positive culture percentage of 46.6% (Table 1). The age of the pregnant women ranged from 25-40 years. Majority (50.6%) of the study participants were in the age group of 30-34 years. The highest UTI were observed at third trimester gestational age (n=103; 57.2%). Table 1 Characteristics of UTI in pregnant women. Variables Age

25-29 years 30-34 years

≥35 years

Gestational period First trimester Second trimester Third trimester

Numbers (n=180)

Percentage

91

50.6

87 2

48.3

1.1

21

11.7

103

57.2

56

31.1

From the 180 isolates, 154 were Gram negative while 26

were Gram positive bacteria (Figure 1). Escherichia coli (E. coli) was the most common organism isolated accounting for 79 (43.9%) and the second highest organism was Klebsiella oxytoca (K. oxytoca) (n=35; 19.4%) followed by Klebiella pneumoniae ( K. pneumoniae ) ( n= 24 ; 13 . 3 % ) . T he other bacterial isolates obtained in the study were Enterococcus faecalis ( E. faecalis ) , Staphylococcus saprophyticus ( S. saprophyticus), Staphylococcus aureus (S. aureus), Proteus mirabilis ( P. mirabilis ) , Proteus vulgaris ( P. vulgaris ) , Pseudomonas aeruginosa (P. aeruginosa), Citrobacter koseri (C. koseri) and Citrobacter amalonaticus (C. amalonaticus). The frequency of occurrence of other bacterial isolates were E. faecalis (n=12; 6.7%), S. saprophyticus (n=10; 5.5%),

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P. mirabilis (n=9; 5.0%), S. aureus (n=4; 2.2%), P. aeruginosa (n=3; 1.7%), P. vulgaris (n=2; 1.1%), C. koseri (n=1; 0.6%) and C. amalonaticus (n=1; 0.6%). 19.4%

E. coli K. oxytoca K. pneumoniae

43.9%

13.3% 6.7%

5.0%

0.6%

0.6%

1.1%

1.7%

5.5%

E. faecalis S. saprophyticus P. mirabilis S. aureus P. aeruginosa P. vulgaris C. koseri

2.2%

C. amfalonaticus

Figure 1. Distribution of bacterial population in pregnant women with UTI.

Antibiotic sensitivity pattern of the bacterial isolates

revealed that E. coli with 89.9% sensitivity to amikacin, 83.5% to co-trimoxazole, 79.7% to clindamycin and 77.2% to ciprofloxacin (Table 2). The antibiotics which had poor activity against E. coli were cloxacillin (13.9%), gentamycin (12.6%), vancomycin (8.9%), erythromycin (7.6%), amoxicillin ( 5 . 1 % ) and oxacillin ( 2 . 5 % ) . K. oxytoca showed 88 . 5 % sensitivity to ciprofloxacin and 62.8% to nalidixic acid while sensitivity to erythromycin was 0%. Most of the antibiotics were effective against K. pneumoniae with co-trimoxazole has significant activity (91.6%) followed by cefotaxime (83.3%). Gross 100% sensitivity was noted on nalidixic acid against E. faecalis and P. mirabilis. S. saprophyticus was 90% sensitive to co-trimoxazole and 80% to nalidixic acid, clindamycin and vancomycin. A complete 100% sensitivity to cefotaxime

and clindamycin was observed with P. aeruginosa, P. vulgaris, C. koseri and C. amalonticus. The isolated uropathogens revealed the presence of high levels of single and multiple antimicrobial resistances against commonly prescribed drugs as shown in Table 3 . A mikacin had the highest overall sensitivity ( n= 138 ; 76.7%) against the 180 isolates tested. This was followed by ciprofloxacin (n=132; 73.3%) and clindamycin (n=124; 68.9%). Cefotaxime and nalidixic acid were exhibited 65.0% and 63.9% sensitivity against the isolates. Ceftriaxone had the overall sensitivity of 52.8%. The other antibiotics were recorded lesser than 50 % of the sensitivity as follows: co-trimoxazole 45.0%, cloxacillin 31.6%, oxacillin 31.1%, norfloxacin 29.4%, vancomycin 28.9%, amoxicillin 28.3%, gentamycin 27.2% and erythromycin 18.3%. Table 3 Antibiotic sensitivity pattern of the isolates. Antibiotics Penicillin Cephalosporin

Frequency

Amoxicillin

51

Cloxacillin

57

Oxacillin

Cefotaxime

Ceftriaxone

Fluoroquinolones Nalidixic acid Ciprofloxacin

Aminoglycosides Macrolide

Lincosamides Glycopeptide Sulfonamide

Norfloxacin Amikacin

Gentamycin

Erythromycin Clindamycin Vancomycin

Co-trimoxazole

Percentages Sensitive Resistance

56

28.3

71.7

31.6

68.4

31.1

117

65.0

115

63.9

53

29.4

95

132

52.8

73.3

138

76.7

33

18.3

49

27.2

124

68.9

81

45.0

52

28.9

68.9 35.0 47.2 36.1 26.7 70.6 23.3 72.8 81.7 31.1 71.1 55.0

Table 2 Antibiotic sensitivity pattern of urinary isolates. n(%). Antibiotic

E. coli

K. oxytoca

4 (5.1)

11 (31.4)

Cloxacillin (5 µg)

11 (13.9)

8 (23.0)

Ceftriaxone (30 µg)

47 (59.5)

Amoxicillin (10 µg) Oxacillin (10 µg)

Cefotaxime (10 µg)

Nalidixic acid (30 µg) Ciprofloxacin (5 µg) Norfloxacin (10 µg) Amikacin (30 µg)

Gentamycin (10 µg)

Erythromycin (10 µg)

2 (2.5)

12 (34.2)

53 (67.0)

17 (48.5)

38 (48.1)

22 (62.8)

45 (56.9)

10 (28.6)

61 (77.2) 71 (89.9) 10 (12.6) 6 (7.6)

8 (22.8)

31 (88.5) 18 (51.4) 5 (14.2) 0 (0.0)

K. E. faecalis S. P. mirabilis S. aureus P. P. vulgaris C. koseri C. pneumoniae saprophyticus aeruginosa amalonticus 8 (33.3) 9 (75.0) 7 (70.0) 7 (77.7) 2 (50.0) 2 (66.6) 0 (0.0) 0 (0.0) 1 (100.0) 16 (66.7)

1 (25.0)

2 (66.6)

0 (0.0)

0 (0.0)

1 (100.0)

7 (58.3)

4 (40.0)

8 (88.9)

1 (25.0)

3 (100.0)

2 (100.0)

1 (100.0)

1 (100.0)

2 (100.0)

1 (100.0)

1 (100.0)

1 (100.0)

1 (100.0)

0 (0.0)

0 (0.0)

7 (58.3)

17 (70.8)

12 (100.0)

14 (58.3)

9 (75.0)

11 (45.8) 19 (79.1) 17 (70.8) 7 (29.1)

18 (51.4)

10 (41.6)

Co-trimoxazole (30 µg)

66 (83.5)

20 (57.1)

22 (91.6)

3 (56.0)

6 (66.6)

15 (62.5)

20 (83.3)

63 (79.7) 7 (8.9)

7 (70.0)

11 (91.6)

Clindamycin (2 µg)

Vancomycin (30 µg)

9 (75.0)

10 (41.6)

18 (75.0)

8 (66.6) 9 (75.0) 4 (33.3) 5 (41.6) 9 (75.0) 8 (66.6)

10 (83.3)

3 (30.0) 6 (60.0) 8 (80.0)

8 (88.9) 8 (88.9)

9 (100.0)

6 (60.0)

8 (88.9)

5 (50.0)

8 (88.9)

4 (40.0) 5 (50.0) 7 (70.0) 8 (80.0) 8 (80.0) 9 (90.0)

6 (66.6) 3 (33.3) 4 (44.4) 6 (66.6) 2 (22.2) 6 (66.6)

3 (75.0)

1 (33.3)

1 (50.0)

0 (0.0)

2 (66.6)

1 (50.0)

2 (50.0)

3 (100.0)

1 (50.0)

3 (75.0)

2 (66.6)

1 (25.0)

2 (66.6)

2 (50.0)

2 (66.6)

3 (75.0) 3 (75.0)

2 (66.6) 0 (0.0)

3 (75.0)

3 (100.0)

3 (75.0)

3 (100.0)

4 (100.0)

1 (33.3)

1 (50.0)

2 (100.0) 1 (50.0) 1 (50.0)

0 (0.0)

1 (100.0) 1 (100.0) 0 (0.0) 0 (0.0)

2 (100.0)

1 (100.0)

2 (100.0)

0 (0.0)

1 (50.0)

0 (0.0)

1 (100.0) 0 (0.0) 0 (0.0)

1 (100.0) 0 (0.0)

1(100.0)

0 (0.0) 0 (0.0)

Sibi G, Pinki Kumari and Kabungulundabungi Neema /Asian Pac J Trop Med 2014; 7(Suppl 1): S116-S120

4. Discussion While treating UTI in pregnancy, proper investigation

and treatment are needed to prevent serious life threatening condition and morbidity rate[17]. In this study, it was observed that most of the uropathogens were same as over the years but the antibiotic resistance pattern were varying and increasing. F emales of the age group between 25 - 34 years were more susceptible to UTIs (98.9%) than the elderly ones. H igh sexual activities, recent use of diaphragm with spermicide are associated with high incidence of UTI in young females[18]. The occurrence of asymptomatic and symptomatic bacteriuria was increased with gestational period as 31.1% in second trimester and 57.2% in third trimester. The Gram negative bacteria were predominated with E. coli being the most common pathogen (43.9%) followed by K. oxytoca (19.4%) in this study. E. coli and Klebsiella spp are most common in each of three trimesters of pregnant women with UTI[19]. Among the Gram positive organisms, E. faecalis and S. saprophyticus were formed the majority of uropathogens isolated. Enterococcus is reported as a frequent cause of UTIs[20]. S. saprophyticus has been found to colonize the urinary tract in earlier reports[21,22]. Most of the E. coli strains were sensitive to amikacin (89.9%) and similar kind of results was seen with Rizvi et al[23]. K. oxytoca was resistant to cefotaxime and ceftriaxone which is in accordance with earlier report where cephalosporin resistant strains were isolated from UTIs[24]. However, K. pneumoniae was highly sensitive to cefotaxime (83.3%) and the findings are similar with previous study[25]. Nalidixic acid and co-trimoxazole were highly effective against E. faecalis with 100% and 83.3% sensitivity. Cephalosporins and quinolones were shown to effective against UTI causing organisms in pregnant women[26]. Antimicrobial susceptibility testing revealed the high resistance to penicillins ( beta lactam group ) by the urinary isolates and similar results were reported in earlier studies[27,28]. This could be a result of extensive usage of these antibiotics and increased spreading of beta lactamase producing strains. This finding restricts the use of beta lactam group of antibiotics though they are considered as traditional drugs safe in pregnancy. Most of the isolates had poor sensitivity to gentamycin (27.2%) which is known to be nephrotoxic[29], and should therefore be avoided. Previous report of trimethoprim as effective

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drug[30] against uropathogens is becoming less effective with only 45% sensitivity from this study. Sensitivity to flouroquinolones especially with ciprofloxacin ( 73 . 3 % ) and nalidixic acid (63.9%) were significant in this study thus revealing their potency against the uropathogens. However, widespread usage may lead to resistance against fluoroquinolones[31]. It was found that the resistance to amikacin and ciprofloxacin were low which suggests that these drugs may be considered as first line agents for treatment of UTIs among the pregnant women. Empirical use of antimicrobials may cause the development of more resistant bacteria which complicates the therapy in UTIs[32]. The results revealed that uropathogens were more resistant to penicillins, macrolides and glycopeptides which restrict their use in treating UTIs. In conclusion, the susceptibility patterns of the urinary isolates suggest the necessity of sensitivity reports before initiation of antibiotic therapy in pregnant women with UTIs. Further, this data would help to formulate antibiotic prescription policies while treating pregnant women. Conflict of interest statement We declare that we have no conflict of interest. References [1] Hummers-Pradier E, Kochen MM. Urinary tract infections in adult general practice patients. Br J Gen Pract 2002; 52(482):

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