Extended-Spectrum β Lactamase Producing Escherichia coli

Yasser Awwade^{* *}Correspondence: Yasser Awwade, Department of Clinical Pathology, Al-Azhar University, Cairo, Egypt, Email:

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Introduction

Escherichia coli are a common cause of community-acquired and nosocomial bacterial infections. Extended Spectrum beta Lactamase (ESBL) producing E. coli infections first occurred in the nosocomial setting then spread to community-acquired infection. It is now a major public health problem (Hawser SP, et al., 2009). Extended Spectrum beta Lactamases (ESBLs) are a heterogeneus group of enzymes responsible for the resistance of enterobacteria to broad spectrum beta lactam antibiotics (Hsieh CJ, et al., 2010). The incidence of infections due to Extended Spectrum β Lactamase (ESBL) producing bacteria has increased rapidly in recent years and poses a worldwide threat to health care (Ben-Ami R, et al., 2009). It is recognized that Egypt has a very high Extended Spectrum β Lactamase (ESBL) rate of 60.9% (Al-Agamy MH, et al., 2006).

The close relationship between Extended Spectrum β Lactamase (ESBL) production and multidrug resistance leaves only a few treatment options for infections commonly caused by Enterobacteriaceae (Hawser SP, et al., 2009). Patients with an infection caused by Extended Spectrum β Lactamase (ESBL) producing bacteria are at risk for therapeutic failure or even death because there is often a delay before the correct antibiotic treatment is given (Schwaber MJ and Carmeli Y, 2007).

The known risk factors for colonization or onset of infection with Extended Spectrum β Lactamase (ESBL) producing Enterobacteriaceae are antibiotic use, prolonged and/or recent hospital stay, severe illness, recent surgery, bladder catheterization or other invasive medical devices, residence in a long-term care facility, international travel, and age 65 years and older (Tham J, et al., 2010; Tangden T, et al., 2010). Poor hand hygiene and lack of food hygiene facilitates the spread of Extended Spectrum β Lactamase (ESBL) producing Enterobacteriaceae (Kaier K, et al., 2009). It is important to identify patients who are at risk for infection with Extended Spectrum β Lactamase (ESBL) producing bacteria, especially in low endemic countries, in order to reduce mortality, to avoid spread of resistant bacteria in hospitals, and to minimize the number of patients receiving unnecessary treatment with broad spectrum antibiotics (Schwaber MJ and Carmeli Y, 2007).

This study was undertaken to determine the prevalence of Extended Spectrum β Lactamase (ESBL) production among nosocomial isolates of E. coli and risk factors associated with contracting this type of infection.

Materials and Methods

A nested case control, hospital based study was conducted for a period of three months (from September 2017 to November 2017). A total number of 192 consecutive, non-duplicates, clinical isolates of E. coli were obtained from the cultures of specimens from patients aged >18 years hospitalised for >48 hours in El-Hussein University Hospitals in Egypt. The source of these isolates was urine (82), wound swap (33), pus exudates (53), sputum (32) and vaginal swab (14). Bacterial isolates of E. coli were subjected to antibiotics susceptibilty testing by disc diffusion technique. The combination disc test using ceftazidime; alone and in combination with clavulanic acid, was performed for the detection of Extended Spectrum β Lactamases (ESBLs) according to Clinical and Laboratory Standards Institute guidelines (Wayne PA, 2010).

Cases were defined as patients diagnosed with Extended Spectrum β Lactamase (ESBL) producing E. coli from September 2012 and November 2012. Controls were randomly selected from the same patients diagnosed with non-Extended Spectrum β Lactamase (ESBL) producing E. coli during the same time period. The following data were collected, age, gender, duration of hospital stay, previous antibiotic therapy, stay in Intensive Care Unit (ICU), presence of invasive device such as urinary catheter or intravenous devices, and use of ventilator or corticosteroid and presence of underlying diseases such as diabetes mellitus, renal failure, liver cirrhosis and malignancy.

Statistical analysis

Data analyses were performed using SPSS, version 12. Categorical variables were compared using Fisher’s exact or Pearson’s chi-square tests where appropriate. The Student’s t-test was used to test for statistical significance of the continuous variables. With 95% Confidence Intervals (95% CI) a P-value of <0.05 was considered statistically significant.

Results

Out of the 192 isolates, 63 (32.8%) were Extended Spectrum β Lactamase (ESBL) producers, and 129 (67.2%) as non-Extended Spectrum β Lactamase (ESBL) producers. Highest ESBLs were found in urine sample (58%) followed by wound swap (22.6%). Ventilator use, increased duration of hospital stay of >7 days and prior use of antibiotics were significantly risk factor for the occurrence of Extended Spectrum β Lactamase (ESBL) producers E. coli (P=0.01, 0.03 and 0.003 respectively).

Distribution of Extended Spectrum β Lactamase (ESBL) positive isolates in different clinical samples showed in Table 1:

Table 1: Distribution of Extended Spectrum β Lactamase (ESBL) positive isolates in different clinical samples

A total of 192 consecutive non-duplicate clinical isolates of E. coli from various clinical specimens collected from different wards of Al-Hussein and Damietta University hospitals. Disk diffusion method detected 63 (32.8%) isolates as Extended Spectrum β Lactamase (ESBL) producers and 129 (67.2%) as non-Extended Spectrum β Lactamase (ESBL) producers. Highest Extended Spectrum β Lactamases (ESBLs) were found in urine sample (58%) followed by wound swap (22.6%).

The results of the risk factor analysis listed in Table 2:

Table 2: Demographic data and risk factors for ESBL-producing E. coli

Mean age ± SD of patients with Extended Spectrum β Lactamase (ESBL) producing isolates was 41.7 ± 19.6 years compared to 39.2 ± 17.4 years for Extended Spectrum β Lactamase (ESBL) non producer patients. There was a significant difference between the Extended Spectrum β Lactamase (ESBL) positive and Extended Spectrum β Lactamase (ESBL) negative groups with regard to prior use of a ventilator (P=0.01), duration of hospital stay >7 days (P=0.03) and prior use of antibiotics (P=0.003) and presence of invasive device and underlying illness were not significant risk factors in this study.

Discussion

Nosocomial infections caused by Multi Drug Resistant (MDR) gram negative bacteria expressing Extended Spectrum Beta lactamases (ESBL) pose serious therapeutic challenge to clinicians due to limited therapeutic options. Our study found that the prevalence of Extended Spectrum β Lactamase (ESBL) producing E. coli was 32.8%. The current study findings are similar to that reported in Saudi Arabia (31.0%) (Memon JI, et al., 2009).

The highest rate of Extended Spectrum β Lactamase (ESBL) production was found in isolates from urine samples (40%), followed by wound swabs (18.75%). This is similar to another study (Kader AA and Kumar A, 2005).

Similar to previous study, the present study showed long hospital stay was significantly associated risk factor for infection with Extended Spectrum β Lactamase (ESBL) producing bacteria (Shanthi M and Sekar U, 2010).

Also prior use of antibiotics prior and use of a ventilator were significant risk factors associated with the occurrence of Extended Spectrum β Lactamase (ESBL). These risk factors were similar to those identified in other studies (Lautenbach E, et al., 2001; Graffunder EM, et al., 2005).

While urinary and vascular catheterization were not significantly associated with Extended Spectrum β Lactamase (ESBL) in our study. Our findings are similar to the findings of few other authors (Harris AD, et al., 2007; Shanthi M, and Sekar U, 2010) while other studies have found the opposite results (Ankur G, et al., 2009; Memon JI, et al., 2009).

Also patient sex, gender, underlying illness and prior use of corticosteroid were not significant risk factors associated with the occurrence of Extended Spectrum β Lactamase (ESBL). Other studies have shown the same results (Memon JI, et al., 2009; Shanthi M, and Sekar U, 2010).

Conclusion

Highest ESBLs were found in urine sample (58%) followed by wound swap (22.6%). Ventilator use, increased duration of hospital stay of >7 days and prior use of antibiotics were significantly risk factor for the occurrence of Extended Spectrum β Lactamase (ESBL) producers E. coli (P=0.01, 0.03 and 0.003 respectively). In this study, we identified ventilator use, increased duration of hospital stay and prior use of antibiotics was associated with the occurrence of Extended Spectrum β Lactamase (ESBL) producers E. coli.

Recommendation

There is a need to review antibiotic prescription practices to reduce the risk of occurrence of Extended Spectrum β Lactamase (ESBL) producers E.coli.

References

1. Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL. Emergence of high levels of extended-spectrum-β-lactamase-producing gram-negative bacilli in the Asia-Pacific region: Data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program, 2007. Antimicrob Agents Che­mother. 2009; 53(8): 3280-3284.

   [Crossref] [Google Scholar] [Pubmed]

2. Hsieh CJ, Shen YH, Hwang KP. Clinical implications, risk factors and mortality following community-onset bacteremia caused by Extended-Spectrum β-Lactamase (ESBL) and non-ESBL producing Escherichia coli. J Microbiol Immunol Infect. 2010; 43(3): 240-248.

   [Crossref] [Google Scholar] [Pubmed]

3. Ben-Ami R, Rodríguez-Baño J, Arslan H, Pitout JD, Quentin C, Calbo ES, et al. A multinational survey of risk factors for infection with Extended-Spectrum β-Lactamase-producing Enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009; 49(5): 682-690.

   [Crossref] [Google Scholar] [Pubmed]

4. Al-Agamy MH, Ashour MS, Wiegand I. First description of CTX-M β-lactamase-producing clinical Escherichia coli isolates from Egypt. Int J Antimicrob Agents. 2006; 27(6): 545-548.

   [Crossref] [Google Scholar] [Pubmed]

5. Schwaber MJ, Carmeli Y. Mortality and delay in effective therapy associated with extended-spectrum β-lactamase production in Enterobacteriaceae bacteraemia: A systematic review and meta-analysis. J Antimicrob Chemother. 2007; 60(5): 913-920.

   [Crossref] [Google Scholar] [Pubmed]

6. Tham J, Odenholt I, Walder M, Brolund A, Ahl J, Melander E. Extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers’ diarrhoea. Infect Dis. 2010; 42(4): 275-280.

   [Crossref] [Google Scholar] [Pubmed]

7. Tängdén T, Cars O, Melhus A, Löwdin E. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum β-lactamases: A prospective study with Swedish volunteers. Antimicrob Agents Chemother. 2010; 54(9): 3564-3568.

   [Crossref] [Google Scholar] [Pubmed]

8. Kaier K, Hagist C, Frank U, Conrad A, Meyer E. Two time-series analyses of the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus infection and Clostridium difficile infection. Infect Control Hosp Epidemiol. 2009; 30(4): 346-353.

   [Crossref] [Google Scholar] [Pubmed]

9. Wayne PA. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 2010; 20: 1-5.

   [Google Scholar]

10. Memon JI, Rehmani RS, Ahmed MU, Elgendy AM, Nizami IY. Extended spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae bacteremia: Risk factors and outcome in the eastern region of Saudi Arabia. Saudi Med J. 2009; 30(6): 803-808.

    [Google Scholar] [Pubmed]

11. Kader AA, Kumar A. Prevalence and antimicrobial susceptibility of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a general hospital. Ann Saudi Med. 2005; 25(3): 239-242.

    [Crossref] [Google Scholar] [Pubmed]

12. Shanthi M, Sekar U. Extended spectrum beta lactamase producing Escherichia coli and Klebsiella pneumoniae: Risk factors for infection and impact of resistance on outcomes. J Assoc Physicians India. 2010; 58: 41-44.

    [Google Scholar] [Pubmed]

13. Lautenbach E, Patel JB, Bilker WB, Edelstein PH, Fishman NO. Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: Risk factors for infection and impact of resistance on outcomes. Clin Infect Dis. 2001; 32(8): 1162-1171.

    [Crossref] [Google Scholar] [Pubmed]

14. Graffunder EM, Preston KE, Evans AM, Venezia RA. Risk factors associated with extended-spectrum β-lactamase-producing organisms at a tertiary care hospital. J Antimicrob Chemother. 2005; 56(1): 139-145.

    [Crossref] [Google Scholar] [Pubmed]

15. Harris AD, Perencevich EN, Johnson JK, Paterson DL, Morris JG, Strauss SM, et al. Patient-to-patient transmission is important in extended-spectrum β-lactamase-producing Klebsiella pneumoniae acquisition. Clin Infect Dis. 2007; 45(10): 1347-1350.

    [Crossref] [Google Scholar] [Pubmed]

16. Ankur G, Prasad KN, Amit P, Sapna G, Ujjula G, Archana A. Extended spectrum β-lactamases in Escherichia coli and Klebsiella pneumoniae and associated risk factors. Indian J Med Res. 2009; 129(6): 695-700.

    [Google Scholar] [Pubmed]