ESBL Positive E. coli and K. pneumoneae are Emerging as Major Pathogens for Urinary Tract Infection

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Original Article INTRODUCTION

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ESBL Positive E. coli and K. pneumoneae are Emerging as Major Pathogens for Urinary Tract Infection Muhammad Abdur Rahim*, Palash Mitra*. Tabassum Samad*. Tufayel Ahmed Chowdhury*. Mehruba Alam Ananna*. Khwaja Nazim Uddin** *Department of Nephrology, **Department of Internal Medicine, BIRDEM, Dhaka, Bangladesh

Background Urinary tract infection (UTI) is the second most common infection through-out the world* Escherichia coli and Klebsiella pneumoneae are responsible for UTI in 90% cases** Extended spectrum beta-lactamase (ESBL) producing E. coli and K. pneumoneae are increasingly being isolated from urine samples Data regarding ESBL positive organisms are limited in our country *Amin M et al. Study of bacteria isolated from urinary tract infections and determination of their susceptibility to antibiotics. Jundishapur J Microbiology 2009; 2(3): 118-123. **Rahman MR et al. Pattern of Bacterial Pathogens Causing Urinary Tract Infection and Their Antibiotic Sensitivity: A Tertiary Care Hospital Experience. Birdem Med J 2015;5(1):20-23.

Objectives To describe the frequency of ESBL positive E. coli and K. pneumoneae causing UTI To describe the associated risk factors To describe the antibiotic sensitivity pattern of these organisms

Materials and Methods Type of study: Cross-sectional study Place of study: Departments of Internal Medicine and Nephrology, BIRDEM General Hospital Period of study: January to March, 2014 Inclusion criteria: One hundred consecutive culture positive UTI cases due to E. coli or K. pneumoneae infection irrespective of their ESBL positivity Exclusion criteria: UTI due to organisms other than E. coli and K. pneumoneae Sampling method: Purposive

Results Total number of Patients Mean age 100 (82% of all culture positive UTI) 59.1±11.7 (18-83) years Male:Female 1:3.3 DM:non-DM 24:1 Mean duration of DM 9.7±4.9 years Mean HbA1c 9.5±2.3% Mean RBS at admission DM= diabetes mellitus 15.7±6.6 m.mol/l RBS= random blood glucose

Co-morbidities (N=100) Co-morbidity Frequency Percentage DM 96 96 Hypertension 58 58 IHD 19 19 CKD 39 39 Stroke 4 4 Dyslipidaemia 42 42 Fatty Liver 19 19 DM= diabetes mellitus IHD= ischaemic heart disease CKD= chronic kidney disease

Presenting features (N=100) Presenting Features Frequency Percentage Fever 94 94 Increased Urinary frequency 42 42 Dysuria 41 41 Loin pain 31 31 Supra-pubic pain 37 37 Incontinence 11 11 Vomiting 72 72 *All patients had >1 sympotoms

Risk factors for infection with ESBL producing organisms Risk factors ESBL positive organisms (n=58) Mean age (years) 59.8 57.5 Non-ESBL positive organisms (n=42) p value Sex Female 41 26 0.358 1.48 Male 17 16 DM Present 56 40 0.741 1.40 Absent 2 2 Duration of DM <5 years 3 5 6-10 years 11 27 0.000 2.48 >10 years 44 10 OR

Risk factors for infection with ESBL producing organisms Risk factors ESBL positive organisms (n=58) Non-ESBL positive organisms (n=42) p value HbA1c <7% 1 6 0.015 9.50 7% or more 57 36 Catheterized Yes 19 5 0.016 3.61 No 39 37 CKD Yes 49 17 0.000 8.01 No 9 25 Renal stone Yes 2 1 0.222 1.46 No 56 41 Past H/O UTI Yes 19 4 0.006 4.63 No 39 38 OR

Risk factors for infection with ESBL producing organisms Risk factors ESBL positive organisms (n=58) Non-ESBL positive organisms (n=42) p value OR H/O antibiotic intake Yes 15 3 0.016 4.53 No 43 39 H/O hospitalization last year Yes 11 2 0.038 4.68 No 47 40

Antibiotic sensitivity and resistance patterns of E. coli (n=84) and K. pneumoneae (n=16) Bacterial organism E.coli n=36 (non- ESBL) (%) E. coli n=48 (ESBL positive) (%) K. sp n=6 (non- ESBL) (%) K. sp. n=10 (ESBL positive) (%) Antibiotic sen res sen res sen res sen res Amikacin 36 0 (0) 47 1 (2.13) 3 (50) 3 (50) 10 0 (0.0) (97.9) Augmantin 0 (0) 36 0 (0) 48 0 (0) 6 0 (0) 10 Cefixime 10 26 0 (0) 48 3 (50) 3 (50) 0 (0) 10 (27.8) (72.2) Ceftazidime 10 26 0 (0) 48 3 (50) 3 (50) 0 (0) 10 (27.8) (72.2) Ceftriaxone 10 26 0 (0) 48 3 (50) 3 (50) 0 (0) 10 (27.8) (72.2) Cefuroxime 10 26 0 (0) 48 3 (50) 3 (50) 0 (0) 10 (27.8) (72.2) Ciprofloxacin 10 26 0 (0) 48 3 (50) 3 (50) 0 (0) 10 (27.8) (72.2) Colistin - - - - 2 0 (0) - -

Antibiotic sensitivity and resistance patterns of E. coli (n=84) and K. pneumoneae (n=16) Bacterial organism E.coli n=36 (non- ESBL) (%) E. coli n=48 (ESBL positive) (%) K. sp n=6 (non- ESBL) (%) K. sp. n=10 (ESBL positive) (%) Antibiotic sen res sen res sen res sen res Co-trimox 10 26 22 26 3 (50) 3 (50) 0 (0) 16 (27.8) (72.2) (45.8) (54.2) Gentamicin 22 14 20 28 3 (50) 3 (50) 10 0 (0) (61.1) (38.9) (41.7) (58.3) Imipenem 36 0 (0) 48 0 (0) 6 0 (0) 10 0 (0) Mecillinam 24 12 18 30 3 (50) 3 (50) 10 0 (0) (66.7) (33.3) (37.5) (62.5) Netilmicin 36 0 (0) 44 4 (8.3) 6 0 (0) 10 0 (0) (91.7) Nitrofurantoin 34 2 (5.6) 43 5 (10.4) 6 0 (0) 0 (0) 10 (94.4) (89.6) Vancomycin - - - - - - - - Piperacilin - - - - - - - - PPC+Tazobac - - - - 0 (0) 2 - - *Not all specimens were tested against all antibiotics listed; sen=sensitive; res=resistant; PPC=piperacilin.

Discussion In one study from Nepal ESBL positivity of E. coli and K. pneumoneae were found to be 13.51% and 16.55% respectively.* In North India 48.27% organisms were confirmed to be ESBL producers, among whom 55.69% were E. coli and 44.31% were K. pneumoniae.** *Chander A et al. Prevalence of extended spectrum beta lactamase producing Escherichia coli and Klebsiella pneumoniae urinary isolates in a tertiary care hospital in Kathmandu, Nepal. BMC Research Notes 2013, 6:487. **Shaikh S et al. Risk factors for acquisition of extended spectrum beta lactamase producing Escherichia coli and Klebsiella pneumoniae in North-Indian hospitals. Saudi J Biol Sci;2015:37-41.

Discussion In Korea, over a six-year period, the proportion of ESBL-EC responsible for causing community-onset bacteremia had increased significantly from 3.6% in 2006 to 14.3% in 2011.* In Central Africa, proportion of ESBL producing Enterobacteriaceae was 15.4% and 49.4% of all K. pneumoniae were ESBL-producer.** *Kang C et al. Clinical and Molecular Epidemiology of Community-Onset Bacteremia Caused by Extended-Spectrum β-lactamase- Producing Escherichia coli over a 6-Year Period. J Korean Med Sci 2013; 28: 998-1004. **Alabi et al. Retrospective analysis of antimicrobial resistance and bacterial spectrum of infection in Gabon, Central Africa. BMC Infectious Diseases 2013, 13:455.

Discussion Length of hospital stay (>3 days) and previous exposure to antibiotics were found as significant risk factors in India. Imipenem and meropenem were suggested as drugs of choice.* Advanced age, diabetes, use of catheters, previous hospitalization and previous antibiotic treatment were some of the risk factors found among patients in Spain.** *Shaikh S et al. Risk factors for acquisition of extended spectrum beta lactamase producing Escherichia coli and Klebsiella pneumoniae in North-Indian hospitals. Saudi Journal of Biological Sciences 2015;22: 37 41. **Ines Rubio-Perez. Extended-spectrum beta-lactamaseproducing bacteria in a tertiary care hospital in Madrid: epidemiology, risk factors and antimicrobial susceptibility Patterns. COACTION 2012; Emerg Health Threats J 2012, 5: 11589 - http://dx.doi.org/10.3402/ehtj.v5i0.11589

Limitations Study period and sample size was small Most patients were diabetic Single center study

Conclusion Two-thirds of the E. coli and K. pneumoneae in this study were ESBL positive Female patients, DM, long history and poor control of DM, past history of UTI, CKD and catheterization were important risk factors for ESBL positivity Aminoglycosides, carbapenems and nitrofurantoin remain the drug of choice All laboratories should routinely screen for ESBL positivity

Thank You All