Open Access

Antimicrobial resistance in community and nosocomial Escherichia coli urinary tract isolates, London 2005 – 2006

Contributed equally
Annals of Clinical Microbiology and Antimicrobials20087:13

DOI: 10.1186/1476-0711-7-13

Received: 03 April 2008

Accepted: 18 June 2008

Published: 18 June 2008

Abstract

Background

Escherichia coli is the commonest cause of community and nosocomial urinary tract infection (UTI). Antibiotic treatment is usually empirical relying on susceptibility data from local surveillance studies. We therefore set out to determine levels of resistance to 8 commonly used antimicrobial agents amongst all urinary isolates obtained over a 12 month period.

Methods

Antimicrobial susceptibility to ampicillin, amoxicillin/clavulanate, cefalexin, ciprofloxacin, gentamicin, nitrofurantoin, trimethoprim and cefpodoxime was determined for 11,865 E. coli urinary isolates obtained from community and hospitalised patients in East London.

Results

Nitrofurantoin was the most active agent (94% susceptible), followed by gentamicin and cefpodoxime. High rates of resistance to ampicillin (55%) and trimethoprim (40%), often in combination were observed in both sets of isolates. Although isolates exhibiting resistance to multiple drug classes were rare, resistance to cefpodoxime, indicative of Extended spectrum β-lactamase production, was observed in 5.7% of community and 21.6% of nosocomial isolates.

Conclusion

With the exception of nitrofurantoin, resistance to agents commonly used as empirical oral treatments for UTI was extremely high. Levels of resistance to trimethoprim and ampicillin render them unsuitable for empirical use. Continued surveillance and investigation of other oral agents for treatment of UTI in the community is required.

Background

Escherichia coli is the predominant cause of both community and nosocomial urinary tract infection (UTI). In the UK, trimethoprim or nitrofurantoin are usually recommended for empirical treatment of episodes of uncomplicated cystitis in the community [1], whilst parenteral cephalosporins and aminoglycosides are reserved for complicated infections or pyelonephritis. In North America a cut off point of 20% has been suggested as the level of resistance at which an agent should no longer be used empirically [2]. A UK study of the antimicrobial susceptibility of bacterial pathogens causing UTI in 1999 – 2000 showed high levels of resistance to trimethoprim, amoxicillin and oral cephalosporins [3] whilst a study of three collections of E. coli strains obtained from patients in East London in 1991, 1999 and 2004 showed rates of trimethoprim resistance of over 30% [4]. The emergence of strains producing extended spectrum β-lactamases (ESBL's) and others exhibiting quinolone resistance now threatens the empirical use of both cephalosporins and ciprofloxacin [5] seriously limiting treatment regimens. In order to determine current levels of resistance to antibiotics commonly used locally for empirical treatment, we reviewed susceptibility to ampicillin, amoxicillin/clavaulanate, trimethoprim, nitrofurantoin, cefalexin, gentamicin, ciprofloxacin and cefpodoxime amongst all E. coli urinary isolates obtained in our laboratory over a 1 year period.

Methods

All E. coli isolates recovered from urine samples submitted for microscopy, culture and sensitivity to the laboratories of Barts and The London NHS Trust between 1st January and 31st December 2005 were included. Samples originating from General practice, Accident and Emergency or other primary care destinations were considered representative of community isolates whilst samples originating from patients hospitalised for 48 hrs or more on general or specialised wards were considered nosocomial.

Primary isolation of strains from urine specimens was performed using chromogenic agar (Mast diagnostics, Bootle, Merseyside) and bacterial counts quantified by inoculation of 0.3 μl of urine onto cystine lactose electrolyte deficient (CLED) agar (Mast diagnostics). Sensitivity testing was performed by the BSAC disc diffusion method using ampicillin (25 μg), cefalexin (30 μg), gentamicin (10 μg), ciprofloxacin (1 μg), nitrofurantoin (200 μg), trimethoprim (2.5 μg), amoxicillin/clavulanate (30 μg) and cefpodoxime (10 μg) discs and isosensitest agar.

Multi-drug resistance was defined in this analysis as resistance to three or more of the following antibiotics: ciprofloxacin, cefpodoxime, amoxicillin/clavulanate and gentamicin.

Differences in the prevalence of antibiotic resistance between groups were analysed using the χ2 test. Strength of association was assessed by calculation of odds ratios with 95% confidence intervals.

Results

A total of 11,865 E. coli isolates were cultured from urine samples over the study period, of these 10,521 (88.7%) were considered community isolates while 1,344 (11.3%) were of nosocomial origin. 10,166 (85.7%) were from women and 1,656 (14.0%) from men (43 sex unknown). 1,227 (10.3%) were from children < 16 years of age.

The frequency of antimicrobial susceptibility of all isolates to the eight antibiotics is shown in tables 1, 2, 3. Nitrofurantoin was the most active agent (94% susceptible) followed by gentamicin (93.7%) and cefpodoxime (92%). Ampicillin and trimethoprim were the least active agents with 55% and 40% of isolates exhibiting resistance respectively.
Table 1

Frequency of antibiotic susceptibility in relation to sex

Antibiotic

Female (n = 10157)

Male (n = 1656)

P

OR (CI95%)

 

n

n (%) Resistant

n

n (%) Resistant

  

Ampicillin

10153

5460 (53.8)

1652

1051 (63.6)

≤0.001

1.50 (1.35–1.67)

Amoxicillin/clavulanate

9178

1139 (12.4)

1491

310 (20.8)

≤0.001

1.85 (1.61–2.13)

Cefalexin

10139

892 (8.8)

1643

321 (19.5)

≤0.001

2.52 (2.19–2.90)

Ciprofloxacin

10137

1038 (10.2)

1649

374 (22.7)

≤0.001

2.57 (2.25–2.93)

Gentamicin

10149

525 (5.2)

1655

214 (12.9)

≤0.001

2.72 (2.30–3.22)

Nitrofurantoin

10134

551 (5.4)

1647

142 (8.6)

≤0.001

1.64 (1.35–1.99)

Trimethoprim

10138

3989 (39.3)

1652

748 (45.3)

≤0.001

1.28 (1.15–1.42)

Cefpodoxime

8512

525 (6.2)

1418

215 (15.2)

≤0.001

2.72 (2.29–3.22)

Table 2

Frequency of antibiotic susceptibility in relation to age

Antibiotic

< 16 years

≥ 16 years

P

OR (CI95%)

 

n

n (%) Resistant

n

n (%) Resistant

  

Ampicillin

1225

763 (62.3)

10484

5694 (54.3)

≤0.001

0.72 (0.64–0.81)

Amoxicillin/clavulanate

1109

143 (12.9)

9480

1296 (13.7)

NS

1.07 (0.89–1.29)

Cefalexin

1225

100 (8.2)

10462

1104 (10.6)

≤0.01

1.33 (1.07–1.64)

Ciprofloxacin

1224

72 (5.9)

10468

1334 (12.7)

≤0.001

2.34 (1.83–2.99)

Gentamicin

1226

44 (3.6)

10482

693 (6.6)

≤0.001

1.90 (1.39–2.59)

Nitrofurantoin

1224

46 (3.8)

10462

643 (6.1)

≤0.001

1.68 (1.24–2.28)

Trimethoprim

1223

566 (46.3)

10471

4129 (39.4)

≤0.001

0.76 (0.67–0.85)

Cefpodoxime

1064

43 (4.0)

8787

691 (7.9)

≤0.001

2.03 (1.48–2.78)

Table 3

Frequency of antibiotic susceptibility among community and nosocomial isolates

Antibiotic

Community

Nosocomial

P

OR (CI95%)

 

n

n (%) Resistant

n

n (%) Resistant

  

Ampicillin

10509

5663 (53.9)

1339

870 (65.0)

≤0.001

1.59 (1.41–1.79)

Amoxicillin/clavulanate

9564

1145 (12.0)

1145

307 (26.8)

≤0.001

2.69 (2.33–3.11)

Cefalexin

10498

876 (8.3)

1327

340 (25.6)

≤0.001

3.78 (3.29–4.36)

Ciprofloxacin

10488

974 (9.3)

1341

441 (32.9)

≤0.001

4.79 (4.20–5.46)

Gentamicin

10505

482 (4.6)

1342

260 (19.4)

≤0.001

5.00 (4.24–5.88)

Nitrofurantoin

10492

556 (5.3)

1332

139 (10.4)

≤0.001

2.08 (1.71–2.53)

Trimethoprim

10492

4103 (39.1)

1341

649 (48.4)

≤0.001

1.46 (1.30–1.64)

Cefpodoxime

8868

504 (5.7)

1103

238 (21.6)

≤0.001

4.57 (3.85–5.41)

Isolates from men were significantly more resistant to all eight agents than isolates from women (Table 1). In particular, resistance to cefpodoxime, gentamicin, ciprofloxacin and cefalexin was observed more than twice as frequently in isolates from men (odds ratios = 2.5). A significant difference between paediatric and adult isolates was seen for all agents except amoxicillin/clavulanate. Resistance to cefalexin, ciprofloxacin, gentamicin, nitrofurantoin and cefpodoxime was more common in adults whilst ampicillin (OR 0.72) and trimethoprim (OR 0.76) resistance was associated with paediatric strains (Table 2).

Nosocomial isolates were more resistant than community isolates to all agents tested. The prevalence of gentamicin (OR 4.93), ciprofloxacin (OR 4.74), and cefpodoxime (OR 4.48) resistance exhibited the most marked differences (Table 3). Patterns of multi-drug resistance are shown in table 4. Ampicillin resistance in combination with trimethoprim resistance was more frequently observed than resistance to the single agent alone, the combination of ampicillin and trimethoprim resistance was also seen in combination with amoxicillin/clavulanate and ciprofloxacin. Resistance to all agents except nitrofurantoin was the most common multi-drug resistant phenotype and was observed in 1.3% of isolates.
Table 4

Distribution of ten most frequently observed antibiotic resistance patterns.

Antibiotic

n

(%)

Susceptible

4290

36.13

AMP, TRI

2180

18.36

AMP

1835

15.46

TRI

691

5.82

AMP, AMC, TRI

292

2.46

AMP, AMC

265

2.23

AMP, CIP, TRI

241

2.03

AMP, AMC, LEX, CIP, GEN, TRI, CPD

164

1.38

AMP, AMC, LEX, CIP, TRI, CPD

98

0.83

AMP, NIT, TRI

95

0.80

Other

1722

14.50

Total

10151

100

AMP; ampicillin, TRI; trimethoprim, AMC; amoxicillin/clavulanate, CIP; ciprofloxacin, LEX; cefalexin, GEN; gentamicin, CPD; cefpodoxime, NIT; nitrofurantoin

Discussion

In the UK most uncomplicated urinary tract infections are treated in the community with short courses of empirical antibiotics. This relies on susceptibility data from local surveillance schemes as in many cases urine samples are only sent for microbiological evaluation following treatment failure, recurrent or relapsing infection. Although the levels of resistance we observed amongst community isolates may therefore overestimate the true rate of resistance in the community, the high levels of resistance to ampicillin and trimethoprim raise concerns over the use of these agents. This was particularly evident amongst isolates from children, which were more likely to exhibit resistance to ampicillin and trimethoprim compared to those from adults. Increased resistance to the other agents in adults is likely to reflect their wider use both empirically and as second line therapies in relapsing, complicated or nosocomial infection. The higher rates of resistance to all agents observed in males are likely to reflect the complicated nature of UTI in men [6]. Infection in this group usually occurs in the setting of underlying anatomical or functional abnormalities or following instrumentation of the urinary tract and the use of prophylactic antimicrobials. Data on resistance rates in E. coli collected at another London teaching hospital from 1995 – 2000 reveal year on year increases in resistance to amoxicillin, cefuroxime, gentamicin and ciprofloxacin [7]. Resistance to comparable agents in 2005 shows marked elevations in resistance to gentamicin (6.3% v 3.2%) and in particular ciprofloxacin (12% v 1.9%). Resistance to cefpodoxime, which may signify ESBL production [8] was seen in 7.4% of isolates overall, often in combination with resistance to quinolones, aminoglycosides and trimethoprim. Although cefpodoxime resistance was more typical of nosocomial isolates, significant resistance was also observed in the community. These isolates most likely represent CTX-M producing strains of E. coli which have disseminated widely throughout Europe post 2000 [9] with those producing CTX-M-15 being most widespread in the UK [10].

Conclusion

Nitrofurantoin remained the most active agent and as it can be administered orally and is highly concentrated in urine, it may therfore be the most appropriate agent for empirical use in uncomplicated UTI. Empirical treatment for nosocomial UTI or infection with multi-drug resistant isolates remains challenging with many authorities recommending parenteral carbapenems (imipenem, ertapenem or meropenem) [11] especially where ESBL producing isolates may be involved. The increasing rates of resistance to uropathogenic E. coli isolates reported worldwide [12, 13] warrants evaluation of other treatments such as fosfomycin [14] or possibly novel cephalosporin/inhibitor combinations [15].

Notes

Declarations

Authors’ Affiliations

(1)
Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry
(2)
Department of Medical Microbiology, Homerton University Foundation NHS trust
(3)
Division of Infection, Barts and The London NHS Trust

References

  1. Baerheim A: Empirical treatment of uncomplicated cystitis. BMJ. 2001, 323: 1197-1198. 10.1136/bmj.323.7323.1197PubMed CentralView ArticlePubMedGoogle Scholar
  2. Gupta K, Hooton TM, Stamm WE: Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann Intern Med. 2001, 135: 41-50.View ArticlePubMedGoogle Scholar
  3. Farrell DJ, Morrissey I, De Rubeis D, Robbins M, Felmingham D: A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection. J Infect. 2003, 46: 94-100. 10.1053/jinf.2002.1091View ArticlePubMedGoogle Scholar
  4. Bean DC, Livermore DM, Papa I, Hall LM: Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man. J Antimicrob Chemother. 2005, 56: 962-964. 10.1093/jac/dki332View ArticlePubMedGoogle Scholar
  5. Potz NA, Hope R, Warner M, Johnson AP, Livermore DM, : Prevalence and mechanisms of cephalosporin resistance in Enterobacteriaciae in London and South East England. J Antimicrob Chemother. 2006, 58: 320-326. 10.1093/jac/dkl217View ArticlePubMedGoogle Scholar
  6. Lipsky BA: Urinary tract infections in men. Epidemiology, pathophysiology, diagnosis, and treatment. 1989, 110: 138-150.Google Scholar
  7. Shannon KP, French GL: Increasing resistance to antimicrobial agents of Gram-negative organisms isolated at a London teaching hospital, 1995 – 2000. J Antimicrob Chemother. 2004, 53: 818-825. 10.1093/jac/dkh135View ArticlePubMedGoogle Scholar
  8. Hope R, Potz NA, Warner M, Fagan EJ, Arnold E, Livermore DM: Efficacy of practised screening methods for detection of cephalosporin-resistant Enterobacteriaceae. J Antimicrob Chemother. 2007, 59: 110-113. 10.1093/jac/dkl431View ArticlePubMedGoogle Scholar
  9. Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, Ayala J, Coque TM, Kern-Zadanowicz I, Luzzaro F, Poirel L, Woodford N: CTX-M: Changing the face of ESBLs in Europe. J Antimicrob Chemother. 2007, 59: 165-174. 10.1093/jac/dkl483View ArticlePubMedGoogle Scholar
  10. Karisk E, Ellington MJ, LIvermore DM, Woodford N: Virulence factors in Escherichia coli with CTX-M-15 and other extended spectrum β-lactamases in the UK. J Antimicrob Chemother. 2008, 61: 54-58. 10.1093/jac/dkm401View ArticleGoogle Scholar
  11. Matsumoto T, Muratani T: Newer carbapenems for urinary tract infections. Int J Antimicrob Agents. 2004, 24 (Suppl 1): 35-38. 10.1016/j.ijantimicag.2004.03.001.View ArticleGoogle Scholar
  12. Alos JI, Serrano MG, Gomez-Garces JL, Perianes J: Antibiotic resistance of Escherichia coli from community acquired urinary tract infections in relation to demographic and clinical data. Clin Microbiol Infect. 2005, 11: 199-203. 10.1111/j.1469-0691.2004.01057.xView ArticlePubMedGoogle Scholar
  13. Hames L, Rice CE: Antimicrobial Resistance of Urinary Tract Isolates in acute uncomplicated cystitis among college aged women: Choosing a first line therapy. J Am Coll Health. 2007, 56: 153-156. 10.3200/JACH.56.2.153-158View ArticlePubMedGoogle Scholar
  14. Pullukcu H, Tasbakan M, Sipahi OR, Yamazhan T, Aydemir S, Ulusoy S: Fosfomycin in the treatment of extended spectrum β-lactamase producing Escherichia coli related lower urinary tract infection. Int J Antimicrob Agents. 2007, 29: 62-5. 10.1016/j.ijantimicag.2006.08.039View ArticlePubMedGoogle Scholar
  15. Livermore DM, Hope R, Mushtaq S, Warner M: Orthodox and unorthodox clavulanate combinations against extended spectrum β-lactamase producers. Clin Microbiol Infect. 2008, 14 (Suppl 1): 189-193. 10.1111/j.1469-0691.2007.01858.xView ArticlePubMedGoogle Scholar

Copyright

© Bean et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement