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Keywords:

  • antibiotic;
  • urinary tract infection;
  • resistance;
  • E. coli

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Study Type – Therapy (practice patterns cohort)

Level of Evidence not applicable

What's known on the subject? and What does the study add?

Epidemiological and resistance patterns of bacterial pathogens in urinary tract infections show large inter-regional variability, and rates of bacterial resistance are continually changing due to different regional antibiotic treatment regime. In Ireland and the UK, trimethoprim or nitrofurantoin is usually recommended for empirical treatment of uncomplicated cystitis in the community whilst parenteral cephalosporins, aminoglycosides, quinolones and co-amoxyclav are reserved for complicated UTIs.

Neither penicillins nor trimethoprim represent suitable empirical antimicrobial agents for UTI in this study population. The high rate of ciprofloxacin resistance in encountered is suggestive of an over-reliance on this agent in this population and with resistance rates approaching 30%, empirical use of quinolones for urology patients is inadvisable. E. coli UTIs have remained extremely sensitive to nitrofurantoin across all three patient sample groups in this population and the resistance rate has not changed significantly over the eleven-year study period.

OBJECTIVE

  • • 
    To investigate the changing pattern of antimicrobial resistance in Escherichia coli urinary tract infection over an eleven year period, and to determine whether E. coli antibiotic resistance rates vary depending on whether the UTI represents a nosocomial, community acquired or urology patient specific infection.

PATIENT AND METHODS

  • • 
    A retrospective analysis of the 42 033 E. coli urine isolates from the 11-year period 1999–2009 in a single Dublin teaching hospital was performed.
  • • 
    WHONETTM software was used to analyse the changing pattern of sensitivity and resistance of E. coli to commonly used antibiotics over the study period.
  • • 
    The origins of the urine samples were stratified into three groups: inpatients with nosocomial UTIs; urine originating from the emergency department and general practice (community UTIs); and UTIs in urology patients.

RESULTS

  • • 
    Urinary tract infections in the urology patient population demonstrate higher antibiotic resistance rates than nosocomial or community UTIs.
  • • 
    There were significant trends of increasing resistance over the 11-year period for ampicillin, trimethoprim, gentamicin and ciprofloxacin, and significant differences in co-amoxyclav, gentamicin, nitrofurantion and ciprofloxacin resistance rates depending on the sample origin.
  • • 
    Ampicillin and trimethoprim were the least active agents against E. coli, with total 11-year resistance rates of 58.3 and 33.8%, respectively.
  • • 
    The overall gentamicin resistance rate was 3.4% and is climbing at a rate of 0.7% per year (P < 0.001). Within the urology patient population the resistance rate was 6.4%.
  • • 
    Ciprofloxacin resistance approaches 20% in the nosocomial UTI population and approaches 30% in the urology population; however, it remains a reasonable empirical antibiotic choice in this community, with an 11-year resistance rate of 10.6%.

CONCLUSIONS

  • • 
    E. coli remains the commonest infecting uropathogen in the community and hospital setting with its incidence climbing from 50 to 60% of UTIs over the 11-year period.
  • • 
    Neither penicillins nor trimethoprim represent suitable empirical antimicrobials for UTI and ciprofloxacin resistance in this Dublin-based study renders it unsuitable empirical therapy for nosocomial UTIs and UTIs in the urology population.
  • • 
    The dramatic 11-year rate increase in gentamicin resistance is of paramount concern.

Abbreviations
MSU

mid-stream urine

EARSS

European Antimicrobial Resistance Surveillance System

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Escherichia coli is the most common organism involved in both community and nosocomial UTI [1]. An international survey of midstream urine samples taken at 252 centres in 17 countries reported that E. coli accounted for 77% of all isolates [2]. E. coli causes ≈80% of community-acquired infections and 40% of nosocomial infections [3]. Klebsiella, Proteus and Enterobacter species are isolated less frequently [4].

Acute, uncomplicated UTIs are most commonly seen in the community and are usually caused by a single bacterial species. Uncomplicated UTI typically affects young women who are immunocompetent and have anatomically normal physiology [5]. The most common clinical manifestation is painful urination stemming from uncomplicated urethritis or cystitis. Complicated UTIs (acute pyelonephritis, pyonephrosis, perinephric abscess, acute prostatitis) often affect patients with underlying functional, metabolic or anatomical defects of the urinary tract, whereas most nosocomial UTIs (≈80%) are related to short- or long-term catheterization [6]. Pathogenic spectrum and antibiotic resistance rates in uncomplicated male and female UTIs are similar, indicating that data from UTI susceptibility studies in women from the same geographic region can be useful in the choice of empirical therapy in men [7]. In Ireland and the UK, trimethoprim or nitrofurantoin is usually recommended for empirical treatment of uncomplicated cystitis in the community [1], whilst parenteral cephalosporins, aminoglycosides, quinolones and co-amoxyclav are reserved for complicated UTIs.

The prevalence of antimicrobial resistance in urinary pathogens is increasing worldwide. In particular, an increase in antibiotic resistance of E. coli has been identified in Europe and North America [8,9]. WHO and the European Union (EU) have recognized the importance of studying the emergence and causes of antibiotic resistance and the need for strategic development to control this public health issue [10,11]. A threshold of 20% has been suggested as the degree of resistance at which an agent should no longer be used empirically [12].

Epidemiological and resistance patterns of bacterial pathogens in UTIs show large inter-regional variability, and rates of bacterial resistance are continually changing due to different regional antibiotic treatment regimes [9,13]. Even in the same country the susceptibility patterns of the micro-organisms exhibit regional differences [14].

In almost all cases of UTI, empirical antimicrobial treatment is initiated before the laboratory results of urine culture are available and thus antibiotic resistance might increase in uropathogens due to frequent inappropriate antibiotic choice [15]. Empirical therapy to treat UTI should be tailored to the surveillance data on the epidemiology and resistance patterns of common uropathogens to reduce treatment failures and emergence of bacterial resistance strains [9,16].

Our study was conducted to evaluate the changing resistance patterns of commonly used antibiotics against nosocomial, community-acquired and urology patient-specific E. coli UTIs during an 11-year period from 1999 to 2009 inclusive. We recognize these three patient groupings as distinct populations and hypothesize a varying rate of antimicrobial resistance depending on the origin of the urine sample. Accurate bacteriological records of culture results and local antibiotic resistance patterns will also provide guidance on empirical therapy before sensitivity patterns are available and should promote evidence-based prescribing practices.

In the Netherlands, national prescribing guidelines in uncomplicated UTI are promoted by the Department of Health [17]. Over a 5-year period, the antibiotic susceptibility of uropathogenic E. coli did not change in female patients with uncomplicated UTI. With respect to the prescription of antimicrobial agents, good compliance with the national UTI guidelines was identified [13].

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The Adelaide and Meath Hospital (AMNCH) is a national tertiary referral centre for urology. In addition, local general practices, serving a community population of 250 000, also utilize the services of the hospital microbiology laboratory.

In the present study, we performed an 11-year retrospective analysis of all positive (N= 78 959) mid-stream urine (MSU) samples (one isolate per patient) processed by the microbiology laboratory at AMNCH for the 11 years 1999–2009 inclusive. We then identified all positive samples where the prominent causative organism was E. coli (N= 42 033).

Each year was analysed separately to establish the changing rates of antimicrobial resistance for the E. coli UTIs over the 11-year period.

WHONET database software was used to analyse the microbiology laboratory data collected. WHONET software provides analysis of antimicrobial susceptibility and resistance test results. The BacLink® data conversion utility facilitated the transfer of data from our existing laboratory information systems into WHONET-compatible data, to avoid the need for double data entry. Both software programs are available for download from http://www.who.int/medicines/areas/rational_use/AMR_WHONET_SOFTWARE/en/.

Each urine sample originated from an individual with symptoms suggestive of a UTI or in whom there was clinical suspicion of an underlying UTI such as in the case of infants or the elderly.

Mid-stream urine samples were obtained from most patients. On occasion, in certain patients (e.g. infants and patients with neuropathic bladders) an ‘in and out’ catheter sample was collected. In the case of nosocomial infections, certain samples originated from patients with indwelling catheters. Only samples from individuals with clinical evidence of UTI were included, and cases of asymptomatic bacterial colonization were excluded.

Laboratory investigation of each sample involved microscopy and quantitative culture. Microscopy was used to identify the presence of white blood cells, red blood cells, casts, epithelial cells, bacteria and other cellular components in the urine.

The clean-catch urine samples obtained from patients were inoculated onto Cystine-Lactose-Electrolyte-Deficient (CLED, Oxoid Diagnostics, Cambridge, UK) and CHROMagar Orientation agar (Oxoid Diagnostics) agar with 1 µL calibrated loops by a semi-quantitative technique.

Culture plates were incubated for 18–24 h at 35°C. A threshold of >105 colony-forming units (cfu/mL) has been suggested as being appropriate in discriminating infection [18] and was defined as a positive culture in most circumstances. In some specified groups of patients <105 cfu/mL samples were sent for antimicrobial susceptibility testing as per the Health Protection Agency's standard methods (http://www.hpastandardmethods.org.uk/documents/bsop/pdf/bsop41.pdf).

The isolated bacteria were identified using Vitek II GN identification cards (Biomerieux, Marcy-l'Étoile, France). The susceptibility of each isolated pathogen to antibiotics (ampicillin, amoxicillin-clavulonate [co-amoxyclav], trimethoprim, nitrofurantoin, cefuroxime, gentamicin, and ciprofloxacin) were determined by Vitek II Antimicrobial Susceptibility testing using the Clinical and Laboratory Standards Institute criteria. Complete resistance and sensitivity data for ciprofloxacin were only available for years 2006–2009 inclusive.

The positive urine samples were segregated into three groups depending on the origin of the individual sample. Samples originated from the offices of referring GPs were grouped with samples arriving at the laboratory from the emergency room. The emergency room samples were from all patients presenting to the unit from the community with symptoms suggestive of a UTI who had an MSU analysis confirming E. coli infection. These samples were grouped as ‘community samples’ and comprise the pathogens seen outside of the hospital setting.

Mid-stream urine samples originating from symptomatic patients seen in the urology outpatient department were grouped with those originating from symptomatic urology ward inpatient samples and together this sample population was labelled ‘urology samples’. These urine isolates originated from male and female patients of all ages, who were quite likely experiencing a complicated UTI (including relapses or recurrences) since they were under the investigation and treatment of the urology service.

We recognize that these do not comprise an absolutely distinct patient cohort as they include samples from patients with recurrent UTIs, pre- and postoperative infected urine samples, samples sent from patients with stone disease etc., but we feel they have enough distinction from the community and nosocomial samples to warrant sub-analysis.

The final patient grouping comprised hospital inpatients with an E. coli-positive MSU sample. These were patients admitted under various specialities, excluding urology, who had an MSU analysed for symptoms or clinical suspicion of a UTI. As these urine samples were limited to those sent more than 48 h after admission, they have thus been grouped as ‘nosocomial samples’[19]. Most samples from both the urology and nosocomial cohorts would be from patients with complicated UTIs.

Statistical analysis of the data was performed using R (v2.11.1) software (http://www.R-project.org). A trend analysis (i.e. regression analysis of each antibiotic per year) was performed. In some instances, a quadratic (i.e. year and year squared) was required to capture a curvilinear rate of growth or decline.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The laboratory processed a total of 368 137 MSU samples over the 11-year period 1999–2009. In all, 78 959 were deemed positive samples with evidence of infection and, of these, E. coli was the causative organism in 42 033 (53.2%) samples. E. coli infections as a percentage of total pathogens causing UTI initially declined in 1999 from a prevalence of 54.6% to one of 48.5% in 2003 followed by an increase to 59.9% in 2009 (Table 1). Each of the positive E. coli samples was grouped depending on the source of the sample into community, nosocomial and urology samples, as discussed previously. Community samples represented the greatest number of positive urine samples (N= 38 530,48.8%) followed by nosocomial samples (N= 32 482, 41.1%) and finally urology samples (N= 7947, 10.1%) (Table 1). E. coli was the causative uropathogen in 61.9% (range 56.8–74.0) of the total community samples, 47.4% (range 42.2–51.9) of the total nosocomial samples and 35.2% (range 31.3–46.1) of the total urology samples.

Table 1.  Number of MSU samples processed per year, positive samples among community, nosocomial and urology samples, and numbers of E. coli causative infections
 Year
19992000200120022003200420052006200720082009Total
Number of MSU samples processed25 83328 52831 13733 11531 96333 93535 66538 88238 27335 78335 02336 137
Total number of positive samples4 0245 3075 6127 0938 0167 6748 6589 0488 9837 3807 16478 959
Number of community samples (% of total positive samples)1 578 (39.2)2 390 (45.0)2 705 (48.2)3 680 (51.9)3 912 (48.8)3 719 (48.5)4 449 (51.4)4 452 (49.2)4 039 (45.0)4 206 (57.0)3 400 (47.5)38 530 (48.8)
Number of nosocomial samples (% of total positive samples)1 753 (43.6)2 090 (39.4)2 165 (38.6)2 543 (35.9)3 272 (40.8)3 143 (41.0)3 366 (38.9)3 814 (42.2)4 242 (47.2)2 744 (37.2)3 350 (46.8)32 482 (41.1)
Number of urology samples (% of total positive samples)693 (17.2)827 (15.6)742 (13.2)870 (12.3)832 (10.4)812 (10.6)843 (9.7)782 (8.6)702 (7.8)430 (5.8)414 (5.8)7 947 (10.1)
Total number of E. coli samples (% of positive samples)2 196 (54.6)2 842 (53.6)2 971 (52.9)3 484 (49.1)3 889 (48.5)3 829 (49.9)4 422 (51.1)4 864 (53.8)4 860 (54.1)4 383 (59.4)4 293 (59.9)42 033 (52.3)
Number of community E. coli samples (% of community samples)1 043 (66.1)1 521 (63.6)1 750 (64.7)2 133 (58.0)2 222 (56.8)2 134 (57.4)2 574 (57.9)2 743 (61.6)2 538 (62.8)2 787 (66.3)2 393 (70.4)23 838 (56.7)
Number of nosocomial E. coli samples (% of nosocomial samples)910 (51.9)1 025 (49.0)989 (45.7)1 074 (42.2)1 396 (42.7)1 410 (44.9)1 564 (46.5)1 849 (48.5)2 062 (48.6)1 410 (51.4)1 709 (51.0)15 398 (36.6)
Number of urology E. coli samples (% of urology samples)243 (35.1)296 (35.8)232 (31.3)277 (31.8)271 (32.6)285 (35.1)284 (33.7)272 (34.8)260 (37.0)186 (43.3)191 (46.1)2 797 (6.7)

The graphical representation of the origin of the E. coli samples (Fig. 1) shows a general increasing trend for both the community and nosocomial samples and a comparatively static number of urology samples over the 11-year period. The total number of E. coli samples reached a peak in 2006 and has subsequently decreased.

image

Figure 1. The origin of the 42 033 E. coli-positive MSU samples, 1999–2009: nosocomial (N= 15 398), community (N= 23838), urology (N= 2797) samples.

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Overall resistance rates for the combined pool of positive E. coli samples (N= 42 033) were plotted for the 11-year period (Fig. 2). A significant increase was identified in the E. coli antibiotic resistance rate for ampicillin, trimethoprim, cefuroxime and gentamicin over the 11-year period (Table 2). Gentamicin and trimethoprim show the highest rate of resistance increase, both 0.7% per year (P < 0.001 and P= 0.018, respectively). The resistance rates for ampicillin and cefuroxime increased at rates of 0.5 and 0.4% per year, respectively (P= 0.006 and P= 0.001). E. coli resistance to nitrofurantoin and co-amoxyclav remained relatively static over the period studied. Ciprofloxacin resistance data are only available for years 2006–2009 inclusive, and show an overall decreasing trend of 0.8% per year, however the figure is not statistically significant (P= 0.52).

image

Figure 2. Escherichia coli antibiotic resistance rates (N = 42 033) and overall trends over the 11-year period.

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Table 2.  The annual rate of change in antibiotic resistance for all E. coli samples over 11 years, 1999–2009
AntibioticRate of change in resistance (% per year)P value
Ampicillin+0.50.006
Trimethoprim+0.70.018
Ciprofloxacin−0.80.52
Co-Amoxyclav+0.090.68
Gentamicin+0.7<0.001
Cefuroxime+0.40.001
Nitrofurantoin−0.060.4

Specific antibiotic resistance was further analysed by separating the urine samples depending on their origin (community, nosocomial and urology) and overall 11-year resistance for each antibiotic was calculated (Table 3). Graphical representations of the changing resistance rates of three sample antibiotics are included in Fig. 3a–c.

Table 3.  Total antibiotic resistance 1999–2009
 Pooled samples (N= 42 033), %Community samples (N= 23 838, %Nosocomial samples (N= 15 398), %Urology samples (N= 2797), %
  • *

    With respect to ciprofloxacin, only data for 4 years (2006–2009 inclusive) are available. When calculating percentages, sample cohorts are as follows: pooled samples, N= 18 400; community samples, N= 10 461; nosocomial samples, N= 7030; urology samples, N= 909.

Total number resistant to ampicillin24 485 (58.3)13 704 (57.5)9 090 (59.0)1691 (60.5)
Total number resistant to trimethoprim14 224 (33.8)7 644 (32.1)5 587 (36.3)993 (35.5)
Total number resistant to nitrofurantoin1 110 (2.6)497 (2.1)451 (2.9)162 (5.8)
Total number resistant to gentamicin1 427 (3.4)607 (2.5)642 (4.2)178 (6.4)
Total number resistant to ciprofloxacin*2 615 (14.2)1 107 (10.6)1 248 (17.8)260 (28.6)
Total number resistant to cefuroxime1 560 (3.7)609 (2.6)793 (5.2)158 (5.6)
Total number resistant to co-Amoxyclav4 919 (11.7)2 418 (10.1)2 143 (13.9)358 (12.8)
image

Figure 3. a, A comparison of E. coli resistance to nitrofurantoin in the three sample groups (community samples, N= 23 838; nosocomial samples, N= 15 398; urology samples, N= 2797). Rates of change of resistance in urology and nosocomial samples are not significant. The rate of change in community samples is significant from 2006 onwards (−0.07% per year, P= 0.02). b, A comparison of E. coli resistance to gentamicin in the three sample groups (community samples, N= 23 838; nosocomial samples, N= 15 398; urology samples, N= 2797). After an initial decline in resistance for both the nosocomial and urology sample groups, there is a significant increase in gentamicin resistance. In the community group there is a significant rise in the resistance rate of 0.5% per year over the 11-year period. c, A comparison of E. coli resistance to ciprofloxacin in the three sample groups (community samples, N= 10 461; nosocomial samples, N= 7030; urology samples, N= 909). Overall, there is an insignificant change in the rates of ciprofloxacin resistance across the three sample groups.

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Nitrofurantoin (Fig. 3a) has total 11-year resistance rates of 2.1, 2.9 and 5.8% in the community, nosocomial and urology groups, respectively. The rates of change in E. coli resistance to nitrofurantoin among the urology and nosocomial sample groups are non-linear and demonstrate no significant change over the 11-year period, but a significant decreasing resistance trend is noted in the community samples (–0.07% per year, P= 0.02) from 2006 onwards.

Gentamicin sub-analysis (Fig. 3b) reveals a definite increasing trend in resistance for both the nosocomial and urology sample groups. After an initial decline in resistance for both groups, there is a significant rise to resistance rates of 7.8 and 15.2% in 2009 respectively (Table 4). In the community group there is a significant rise in the resistance rate of 0.5% per year over the 11-year period, reaching 4.8% resistance in 2009. Gentamicin is the antibiotic of choice used in local operative urology prophylaxis.

Table 4.  Rate of change of antibiotic resistance to E. coli in the three sample groups during 1999–2009
 Annual change in percentage resistance, % (P values for coefficients)
TrimethoprimCiprofloxacinCo-amoxyclavGentamicinNitrofurantoin
LinearQuadraticLinearQuadraticLinearQuadraticLinearQuadraticLinearQuadratic
Urology samples−13220.33−0.99n/a−0.03n/a−558+0.14+0.02n/a
(0.048)(0.004)(0.79)(0.91)(0.04)(0.04)(0.907)
Nosocomial samples−10430.26+2.9n/a+0.36n/a−437+0.11−0.07n/a
(0.004)(0.004)(0.13)(0.36)(0.02)(0.02)(0.44)
Community samples+0.8n/a−0.36n/a−0.06n/a+0.5n/a+280−0.07
(0.02)(0.65)(0.77)(<0.005)(0.02)(0.02)

Figure 3c shows a significantly higher resistance rate to ciprofloxacin in E. coli UTIs within the urology group, with an overall 4-year resistance rate of 28.6%. The 4-year resistance rate in the nosocomial group approaches 20% but within the community sample group, it remains relatively static at 10.6%. There is an insignificant increasing rate of resistance identified in the nosocomial group (2.9% per year, P= 0.13).

The overall 11-year resistance rates for co-amoxyclav are highest in the nosocomial group followed by the urology groups at 13.9 and 12.8%, respectively. The lowest rate is seen in the community sample group at 10.1%. For co-amoxyclav the resistance rates decreased in the urology and community sample groups and decreased in the nosocomial group, however the trends are not significant.

In general, we see the highest proportion of antibiotic-resistance E. coli UTIs in the urology sample population followed by the community population. The single exception is with co-amoxyclav, where the nosocomial UTI sample population has a higher total 11-year resistance rate than the urology sample population (13.9 vs 12.8%).

Ampicillin and trimethoprim sub-analysis is omitted as their high resistance rates (58.3 and 33.8%, respectively) indicate they are no longer appropriate first-line empirical therapies for E. coli UTI treatment.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

The increasing prevalence of antibiotic resistance is a serious public health concern. Improved local and regional antimicrobial surveillance is necessary to address this problem and develop local prescribing guidelines.

In general, a higher rate of resistance is noted in the urology sample population than in either the nosocomial or community populations. We propose that this trend is identified because the urology samples are more likely to originate from patients with complicated UTIs associated with calculus disease, congenital anatomical abnormality, LUTS and other urological problems. This patient population is likely to have had an increased exposure to antibiotics because of recurrent previous infections, urological instrumentation, urological procedures, etc., thus increasing resistance rates [20]. Community samples show the lowest resistance rates because this population comprised mainly uncomplicated antibiotic-naïve UTIs in an otherwise healthy population.

The European Antimicrobial Resistance Surveillance System (EARSS) is a publicly funded network for monitoring antimicrobial resistance in the European region. It is a European-wide network of national antibiotic surveillance systems, providing reference data on antimicrobial resistance for public health purposes. EARSS collects routinely generated antimicrobial susceptibility data, and provides spatial trend analyses. Routine data for major indicator pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, E. coli, Klebsiella pneumonia and Pseudomonas aeruginosa) are quarterly submitted by almost 900 laboratories serving more than 1500 hospitals in 33 European countries. The latest EARSS report from 2008 published antibiotic resistance rates from 33 submitting countries (including Ireland) for E. coli UTIs [21].

The 2008 ampicillin resistance rate in the present study was 66%. Most countries reported resistance proportions >50%, but eight countries reported lower resistance proportions. Even in these countries, aminopenicillins have lost their position as the empirical treatment for E. coli infections. Moreover, 14/33 countries reported <5% resistance to third-generation cephalosporins. This proportion has been increasing over the last 4 years in 19 countries. In 2008, two east European countries reported proportions higher than 25% (Bulgaria, 29%; Turkey, 42%). Our analysis focuses on a second-generation cephalosporin cefuroxime, and the 2008 resistance rate is 5.3%. We have similarly also identified a highly significant increase in the cefuroxime resistance rate over the study period of 0.4% per year.

Concerns exist about emerging fluoroquinolone resistance. This has consistently and substantially increased over the past 7 years all over Europe. In 2008, only four countries reported rates <5% [21]. Ten countries report fluoroquinolone resistance rates >25%, with three countries reporting resistance proportions >35% (Italy, 38%; Cyprus, 45%; and Turkey, 52%). In the present study, we identified an overall fluoroquinolone (ciprofloxacin)-resistant E. coli rate of 15% in 2008. However, the mean 4-year (2006–2009) resistance rate is 28.4% within the urology group, 18.1% within the nosocomial sample group and 10.6% within the community sample group. The higher quinolone resistance rate within the nosocomial samples compared with the community samples is similar to findings in a South Korean study [22]. The prevalence of fluroquinolone-resistant E. coli strains as a cause of uncomplicated UTI is increasing in the Netherlands [13], the US [14] and Spain [23]. However, we identified a decreasing rate of –0.36% per year for ciprofloxacin resistance in community E. coli UTIs, but the pattern is not significant and is limited by only 4 years of data. A US-based study of UTIs in the emergency department showed that rates of fluoroquinolone-resistant E. coli infection appear to be low among patients with uncomplicated UTIs but higher among those with complicated infections (1 vs 5%) [24]. Although the resistance rates in our study are higher, they maintain the difference between the uncomplicated (community) and complicated (nosocomial and urology) UTIs.

A Swiss study looking at E. coli UTIs specifically from a urology department showed ciprofloxacin-resistant E. coli in 22% of patients [25], which is lower than the present study's mean 11-year rate of 28.4%. Risk factors for ciprofloxacin-resistant E. coli included prior use of fluoroquinolones, prior urinary tract catheterization and recurrent UTIs. Similarly, Nys et al.[26] looked at trends in antimicrobial susceptibility of E. coli isolates from urology patients in four regions of the Netherlands between 1998 and 2005. Unlike our findings, antibiotic resistance was relatively constant over time for most agents tested, except for piperacillin and the fluoroquinolones. Another Dutch study compared isolates from 10 intensive care units and 10 urology services. Intensive care units had higher resistance rates for co-amoxyclav, cephalosporins and lower resistance rates for nitrofurantoin, trimethoprim and quinolones than urology services [27]. Similarly, in the present study we have identified a higher overall resistance rate in the nosocomial sample group than the urology sample group for co-amoxyclav, and a lower overall resistance rates for all other antibiotics in the urology sample group.

Six European countries reported <5% resistance against aminoglycosides, with the lowest rate identified in Sweden (2%) [21]; 16 countries reported resistance between 5 and 10%. The overall 11-year resistance rate in the present study is 3.4%. Aminoglycoside resistance was also identified as increasing over the last 4 years in 16 countries [21]. The present study identifies a concerning overall significant increase in gentamicin resistance of 0.7% per year. Sub-analysis of the sample populations indicated the rate is increasing significantly for all three groups, particularly the community group (0.5%/year, P < 0.005). Gentamicin represents the antibiotic prophylaxis of choice in our department for invasive urological procedures and this resistance trend is of considerable concern. We are considering a change to prophylactic amikacin for urological procedures based on these data. Such a change has been successfully trialled in London, where local urology services identified a similar gentamicin resistance trend [28].

The EARSS does not provide information on trimethoprim or nitrofurantoin resistance. The present study identifies a total 11-year trimethoprim resistance rate of 33.8% in the pooled E. coli UTI population. This observation is in accordance with previous European data [2]. The community sample group has a total 11-year resistance rate of 32.1%, with the highest increase in resistance rate over the period (0.8% per year P= 0.02). Similarly, in a New Zealand-based study, although overall E. coli resistance to trimethoprim is lower than in the present study, they identified an increasing trend in trimethoprim resistance [29]. Local prescribing guidelines suggest it as first-line empirical therapy for uncomplicated UTI, which has undoubtedly contributed to this. The Infectious Diseases Society of America guidelines recommend trimethoprim as a first-line agent for empirical therapy of uncomplicated UTI only in situations where the resistance rate is <20% [5].

Escherichia coli UTI remains extremely sensitive to nitrofurantoin across all three sample groups and the resistance rates have not changed over the 11-year study period. The highest resistance rate is seen in the urology sample group (5.8%) and we suspect this is because this population is likely to include individuals with prior exposure to antibiotics. This group would be inclusive of sub-populations treated with suppressive antibiotic therapies, including prophylactic courses of nitrofurantoin. As expected, the lowest antibiotic resistance is seen in the predominantly antibiotic-naïve community group.

The ECO.SENS study investigated the prevalence and antimicrobial susceptibility of pathogens causing community-acquired acute uncomplicated UTIs in 4734 women aged 18–65 years in Europe plus Canada [2]. Resistance in E. coli occurred most frequently to ampicillin (30%), followed by trimethoprim (15%) and nalidixic acid (5%) but was low in respect of co-amoxyclav, nitrofurantoin, gentamicin and ciprofloxacin, all at <3%. We have identified similarly low rates in the community E. coli samples for nitrofurantoin and gentamicin, but higher resistance rates for co-amoxyclav, gentamicin and ciprofloxacin.

The North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study determined the antibiotic susceptibility to commonly used agents for UTIs of outpatient E. coli urinary isolates obtained from various geographic regions in the USA and Canada [30]. Comparing this contemporary American study to the total 11-year community sample resistance rates from the present study, resistance to trimethoprim (21.3 vs 32.1%), nitrofurantoin (1.1 vs 2.1%), and ciprofloxacin (5.5 vs 10.6%) was lower in the American group than in this Irish population. It is evident that the sensitivity patterns show significant geographical variation, and thus prescribing guidelines from individual countries are not immediately applicable to other regions. However, the general trends of antimicrobial resistance are similar in both Europe and North America.

A previous pilot study of E. coli UTI in the community in the west of Ireland has identified similar significant resistance to trimethoprim and ampicillin and recommends they are unsuitable empirical antibiotic choices in UTI [31]. However, in their study, E. coli remained susceptible to nitrofurantoin (96.7%), nalidixic acid (93.9%) and ciprofloxacin (94.7%). The present, much larger study clearly identifies higher rates of antibiotic resistance and further shows the inter-regional variability in antibiotic resistance.

This group also looked at local trimethoprim and ciprofloxacin prescribing and the development of resistance of in uropathogenic E. coli in general practice in the west of Ireland [32]. They concluded that a higher amount of antimicrobial prescribing is associated with a higher probability of a resistant E. coli for the patient. The variation in antimicrobial resistance between practices was relatively higher for ciprofloxacin than for trimethoprim. Multiple studies have demonstrated a strong correlation among local prescribing habits, antibiotic consumption and the development of antibiotic resistance in uropathogens. A pan-European study demonstrated that consumption of broad-spectrum penicillins correlated with resistance to ampicillin and there was a clear correlation between quinolone consumption and resistance to ciprofloxacin and nalidixic acid. The strong correlations between prescribing practices and resistance emphasize the importance of controlling antibiotic usage and providing local prescribing guidelines [2].

In conclusion, insight into antimicrobial resistance patterns over time and the emergence and development of de novo resistance are essential for the development of evidence-based therapeutic antibiotic prescribing guidelines. The present study is a retrospective analysis of changing E. coli antimicrobial resistance within a specific geographical region of Ireland, and as such the results might not reflect the resistance patterns experienced in other catchment areas, both within Ireland and in the wider world. However, local resistance patterns are essential knowledge because of the significant inter-regional variation, and prescribing guidelines must be tailored to the regional surveillance data.

Physicians should choose empirical antibiotic therapy based on patient demographics/medical history, presumed aetiology and local resistance patterns. The present study shows the importance of identifying each UTI as representing a community UTI, a nosocomial UTI or a UTI within a urological patient. These populations have varied resistance patterns, which should guide empirical prescribing.

Most (56.7%) of the E. coli samples analysed in the present study represent community UTIs. While no published guidelines exist advising Irish GPs on first-line empirical antimicrobial agents, the present study clearly indicates nitrofurantoin (overall resistance rate 2.1%) and oral cephalopsorins (resistance rate 2.6%) to be appropriate first-line agents. Ciprofloxacin remains a reasonable second-line choice, as does co-amoxyclav. These data will enable evidence-based education community prescribing guidelines to be created, and by educating and altering community prescribing habits we expect to control emerging resistance patterns.

E. coli UTIs within the urology patient population generally exhibit the highest amounts of antibiotic resistance. Of particular concern is the increasing rate of gentamicin resistance in the urology patient population. This trend is of particular concern locally where gentamicin is our prophylactic antibiotic of choice. The high rate of ciprofloxacin resistance is suggestive of an over-use of this agent in this population, and with resistance rates approaching 30%, empirical use of quinolones in the urology population is inadvisable. Within the nosocomial UTI population, E. coli remains extremely sensitive to nitrofurantoin, cefuroxime and gentamicin with resistance rates of <5%; however, of concern is a significant increasing rate of ciprofloxacin and co-amoxyclav resistance.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

We thank Dr Alan Kelly for his assistance in the statistical analysis.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES