1. Antibiotic Resistance in Community Acquired Bacterial
Urinary Tract Infection (UTI) in Bengali Children:
A Rising Challenge
Aniruddha Ghosh,
Sumon Poddar, Jaydeep Choudhury, Maya Mukhopadhyay,
Sushmita Banerjee
Departments of Pediatric Medicine, Pediatric Nephrology & Microbiology
Institute of Child Health, Kolkata, India

2. Pediatric UTI: What we knew

3. The first peak of UTI is in the first year of life
The most frequent serious bacterial infection during childhood
Affecting approximately 2% of boys and 8% of girls by the age of 7 years
Montini et al. N Engl J Med
Roberts et al. Pediatrics
The first peak of UTI is in the first year of life
The second peak of UTI occurs between the ages of 2 to 4 years during toilet training.
After the age of 6 years, UTIs are infrequent.
-Keren et al (RIVUR study). Pediatrics

4. Why are we concerned ?

5. of UTI has not been systematically studied.”
“The risk of renal scarring in children with a first episode
of UTI has not been systematically studied.”
Among children with an initial episode of UTI
57% (95% confidence interval [CI]: 50–64) had changes consistent with
acute pyelonephritis on the acute-phase DMSA renal scan.
15% (95% CI: 11–18) had evidence of renal scarring on the follow up DMSA scan.
Shaikh et al .
Risk of Renal Scarring in Children With a First Urinary Tract Infection:
A Systematic Review [of 1533 articles].
Pediatrics. 2010;126(6):

6. our antibiotic therapies ?
Then what’s hampering
our antibiotic therapies ?

7. varying prevalence and complications of UTI in different races.
The etiology of pediatric UTI and the antibiotic susceptibility of urinary pathogens in both the community and hospitals have been changing.
In recent years drug resistance has become a major problem worldwide while treating pediatric UTI.
Sefton AM. Int J Antimicrob Agents. 2000.
- Gupta K. Infect Dis Clin North Am. 2003.
UTI occurs in all races, but epidemiological studies show
varying prevalence and complications of UTI in different races.
- Heffner et al.Clinical Pediatr Eme Med

8. Objectives of the study:

9. To study the locally prevalent community acquired bacterial uropathogens among hospitalised children and their resistance patterns.

10. Materials & Methodology

11. STUDY DESIGN: Hospital based prospective study
STUDY PERIOD : October 2014 to April 2016 [18 months]
STUDY POPULATION : Infants & Children up to 12 years of age admitted at
Our hospital [located in Kolkata, West Bengal, India]
STUDY AREA: Indoors of a tertiary care referral hospital

12. Unexplained fever (without other definite focus)
SAMPLE SIZE: patients
INCLUSION CRITERIA
EXCLUSION CRITERIA
Unexplained fever (without other definite focus)
Critically ill children with antibiotics prior to urine sampling
Specific symptoms of UTI (dysuria, frequency, abdominal pain, flank pain etc.)
Previous history of UTI
Neonates or infants with suspected sepsis ( poor feeding, vomiting, irritability etc.)
Known structural or functional anomalies of the urinary tract or On antibiotic prophylaxis
Indwelling catheter in situ

13. UTI which can be managed at OPD basis
UTI which are treated in general ward
Urosepsis
requiring ICU care & CAUTI

14. Freshly voided midstream clean catch specimens for older children and suprapubic aspiration specimens in infants were submitted to the clinical microbiology laboratory for processing.
Semi quantitative urine culture using calibrated loop was used to inoculate Blood agar and MacConkey plates.
Isolates were identified by Gram stain, motility test and routine biochemical reactions. Antibiotic sensitivity was put up by the Kirby Bauer modified disc diffusion method following the clinical laboratory standard institute (CLSI) guidelines.
E.coli ATCC 25922, S. aureus ATCC and P. Aeruginosa ATCC were used as quality controls.

15. Results & Analysis

16. CULTURE POSITIVITY: 132/ 1109 (11.9%)
SAMPLES EXCLUDED:
SAMPLES INCLUDED FOR ANALYSIS:
COMMON CLINICAL FEATURES AT PRESENTATION:

17. Gram Negative Organisms Gram Positive Organisms
Table : Distribution of Isolated Organisms depending on Age groups and Gender
Age
0-1 Year
(n=31)
>1-5 Years
(n=40)
>5 Years
(n=26)
Total
(n=97)
Gender
Male
Female
Gram Negative Organisms
E. coli 10 6 20 3 14 59
Klebsiella sp - 2 1 9
Pseudomonas sp 4
Proteus mirabilis
Acinetobacter sp
Gram Positive Organisms
Enterococcus sp 19
Staphylococcus aureus 17 29 11 8 18 97

18. 93%
88%
86%
84%
86%
82%
84%
71%
66%

19. 49%
27%
24%
12%
10%
10% 9% 7%

20. Frequency (proportion)
Table: Resistance against E.coli (n=59) displayed by the No. of different groups of antibiotics
Number of group(s)
Frequency (proportion)
95% Confidence Interval
4 or More
45 (76.27 %)
64.02%-85.3%
3 groups
5 (8.47 %)
3.67%-18.35%
2 groups
4 (6.78 %)
2.67%-16.18%
Only 1 group
Resistance to none
1 (1.69 %)
0.30%-8.99%

21. 89%
78%
67%
56%
44%
44%
33%
33%
22%
11%
11% 0%

22. 100%
75%
75%
50%
50%
25%

23. Enterococcus sp (N=19) & Staphylococcus aureus (N=3)-
Antibiotic resistance pattern
Badhan et al Ind J Urol same percentage of gram positive. Rising trend recently.

24. This is the first study of its kind in recent times from Eastern India.
Gram negative organisms specially E.coli (isolated in 60% of our samples) are consistently the most common uropathogens irrespective of region, race and community or hospital setting .¹ ² ³
Thus changing resistance patterns of E.coli are of paramount importance in planning empiric treatment guidelines for UTI.
The extremely low susceptibility of Gram negative organisms to orally available antibiotics like Fluoroquinolones, Amoxicillin-Clavulanic acid, Cefixime and Cotrimoxazole has been demonstrated in our study.
¹ Kalantar E, Motlagh M, Lornejad H, Reshadmanesh N. Prevalence of urinary tract pathogens and antimicrobial susceptibility patterns in children at hospitals in Iran. Iran J Clin Infect Dis. 2008; 3:149‑53.
² Mashouf RY, Babalhavaeji H, Yousef J. Urinary tract infections: bacteriology and antibiotic resistance patterns. Indian Pediatr. 2009 Jul;46(7):
³ Brad GF, Sabau I, Marcovici T, Maris I, Daescu C, Belei O et al. Antibiotic resistance in urinary tract infections in children. Jurnalul Pediatrului.
2010;13 (5152):73–77.

25. The high percentage of resistance to oral and intravenous Cephalosporins displayed by all Gram negative organisms specially E.coli (>80%), has not been observed in previous publications, particularly when considering community acquired pathogens.
E.coli isolates in our study showed a high degree of multidrug resistance (91.53%) defined as resistance to two or more different antibiotic groups.
when compared to reports from Spain (20.6%) and the United States (7.1%) [14, 15].

26. Another important finding is the high (66
Another important finding is the high (66.1%) resistance to Meropenem among E.coli isolates, which were often susceptible only to antibiotics like Amikacin, Piperacillin-Tazobactam, Imipenem, Cefoperazone-Sulbactam and Polymyxins.
These findings are contrary to studies from Africa, South Asia and some Middle East countries which showed that imipenem, piperacillin-tazobactam and amikacin are less potent against Gram negative organisms [10, 12, 13].

27. Over the counter drugs & Antibiotics abused by anxious parents
Overuse of antibiotics by community healthcare physicians
E.coli resistance has been progressing for more than a decade [16]. In our country, antibiotics are easily available over-the-counter and commonly misused by patients and physicians for trivial symptoms, most commonly due to viral illnesses. In the absence of strict control over antibiotic usage, erratic dosing and inadequate durations of therapy are common. In addition, with increasing resistance patterns to ampicillin and co-trimoxazole, physicians in India started using quinolones and cephalosporins indiscriminately, as first line agents for suspected UTI. However as ours and other studies demonstrate, resistance is fast emerging against these drugs too [17]. A study conducted by NK Ganguly et al [18] documented that between 2005 and 2009 the sale of antibiotics jumped by about 40% with the sale of cephalosporins strikingly increasing by about 60%. Thus the reason for this high level of antibiotic resistance in our study is likely to be due to misuse of antibiotics in our region [2]. An added reason may be that only patients ill enough to require admission were included, in comparison to several other studies that focussed on out-patients also.

29. Nat. Rev. Urol. doi:10.1038/nrurol.2015.199
Figure 3 Global epidemiology of resistance in Gram-negative uropathogens—third-generation cephalosporins
Figure 3 | Global epidemiology of resistance in Gram-negative uropathogens—third-generation cephalosporins. Prevalence of resistance to third-generation cephalosporins in Enterobacteriaceae isolated from patients with urinary infections by country. Data obtained from studies published 2009–2014. The accuracy of these prevalence estimates is affected by the number and heterogeneity of studies undertaken in each country, and reflects resistance data from clinical isolates, which only represent a subset of the total resistance burden in colonized patients.
Zowawi, H. M. et al. (2015) The emerging threat of multidrug-resistant Gram-negative bacteria in urology
Nat. Rev. Urol. doi: /nrurol

30. Nat. Rev. Urol. doi:10.1038/nrurol.2015.199
Figure 2 Global epidemiology of resistance in Gram-negative uropathogens—Fluoroquinolones
Figure 2 | Global epidemiology of resistance in Gram-negative uropathogens—fluoroquinolones. Prevalence of resistance to fluoroquinolones in Gram-negative urinary pathogens by country. Data obtained from studies published 2009–2014. The accuracy of these prevalence estimates is affected by the number and heterogeneity of studies undertaken in each country, and reflects resistance data from clinical isolates, which only represent a subset of the total resistance burden in colonized patients.
Zowawi, H. M. et al. (2015) The emerging threat of multidrug-resistant Gram-negative bacteria in urology
Nat. Rev. Urol. doi: /nrurol

31. Global epidemiology of resistance in Gram-negative uropathogens— Carbapenems

32. What is our suggestion ?

34. 95.5%
77.3%

35. For each and every febrile child admitted in a hospital, sending urine samples for culture & sensitivity study before starting empiric antibiotic therapy is essential.
For parenteral therapy, amikacin or piperacillin-tazobactam may be the first line options while drugs like imipenem, Colistin etc. should be reserved only for those who are critically ill.
It should be pointed out however, that Aminoglycosides are nephrotoxic and should be avoided in patient with renal compromise. Unfortunately in our country, Aminoglycosides blood levels are rarely available to guide therapy, however single daily doses have been reported to be less nephrotoxic [22].

36. Nitrofurantoin remains an oral option in the treatment of UTI
Nitrofurantoin remains an oral option in the treatment of UTI. However it should not be used in upper urinary tract infection as described by many authors but may be used in routine prophylaxis as Cotrimoxazole is showing high resistance against both Gram positive & negative uropathogens.
Antibiotic therapy should be appropriately adjusted and ideally narrowed and scaled down once bacterial sensitivity reports are available.

37. This study is limited by including only patients from A SINGLE CENTRE.
Limitations
This study is limited by including only patients from A SINGLE CENTRE.
Additionally there may be IN-VITRO and IN-VIVO DIFFERENCE in antibiotic susceptibility and we plan future studies to examine the clinical effects of antibiotic therapy in UTI and compare that with the laboratory data.

38. Conclusion:
There is dire need of developing periodic regional bacteriological
surveillance programmes to guide empiric antibiotic therapy.
The aim should be to treat the infection effectively, but at the
same time to avoid causing even further bacterial resistance.
Strict control over antibiotic usage is of paramount importance
to prevent antibiotic abuse and overuse.

39. Thank you for your attention