1 Department of Medical Microbiology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht; 2 Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam; 3 Department of Medical Microbiology, University Hospital Groningen, Groningen, The Netherlands
Received 8 October 2002; returned 8 November 2002; revised 19 January 2003; accepted 20 January 2003
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Abstract |
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Methods: Faecal samples were obtained on admission to the hospital, at the time of discharge, and 1 and 6 months after discharge. All samples were examined for resistance to nine antibiotic agents.
Results: For the total patient population, no significant differences in the prevalence of resistance were observed at the different sampling intervals, except for a significant decrease in cefazolin resistance between the time of discharge and 6 months after discharge (10% to 3%, P < 0.05). This decrease was mainly observed in patients from the university hospital Maastricht (azM), in which a significant decrease from 17% to 6% was detected (P < 0.05). Moreover, despite dissimilarities in patient characteristics and the marked variations in antibiotic use, no significant differences in the prevalence of antibiotic resistance were observed between the three hospitals, except for the overall higher prevalence of cefazolin-resistant E. coli in azM patients (P < 0.05).
Conclusion: In this study, hospitalization did not seem to have any substantial effect on the prevalence of antibiotic-resistant E. coli at the different time intervals. However, as our study population consisted of surgical patients with a relatively moderate antibiotic use, and the prevalence of antibiotic resistance was only analysed for faecal E. coli, further investigation should be encouraged, as the understanding of the interaction between different resistance reservoirs is important for directing future intervention studies.
Keywords: antibiotic resistance, hospitalization, community, E. coli, faecal flora
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Introduction |
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In this study, the impact of hospitalization on the prevalence of resistance in E. coli of the intestinal flora of surgical patients of three university-affiliated hospitals in The Netherlands was analysed prospectively. The prevalence of resistance was determined on admission, at time of discharge and 1 and 6 months after discharge. E. coli was used as an indicator organism, as this species is one of the dominant facultative aerobically growing bacteria of the intestinal flora.
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Materials and methods |
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From 1999 to 2001, patients admitted to the participating surgical wards of the university hospitals of Groningen (azG), Maastricht (azM) and Rotterdam (azR), The Netherlands, were asked to participate in the present study. Upon inclusion, patients were requested to collect a faecal sample at the following time intervals: within 24 h after admission to the hospital, at time of discharge, and 1 and 6 months after discharge. Data on antibiotic use and hospitalization in the 3 months before hospital admission were recorded. At the time of discharge, the reason for surgical admission, the length of stay and the antibiotics prescribed were registered for each patient. Patients were not eligible for the study if they were referred from a nursing home or from another hospital ward. Patients were withdrawn from the analysis if no faecal samples were obtained on admission, at time of discharge or 1 month after discharge, if they stayed for <2 days in the hospital, or if they were referred to an intensive care unit for >24 h after surgery. Approval of the Medical Ethics Committees was obtained before the start of the study. Only patients who had given their informed consent were included in the study.
Sample processing
The prevalence of antibiotic resistance was determined, as described previously.3 In short, after thawing, the samples were further diluted (102104) and 0.04 mL of these dilutions were spread over EosineMethylene Blue (EMB) agar plates (Oxoid CM 69, Basingstoke, UK) with and without antibiotics, using a spiral plater (Salm and Kipp, Utrecht, The Netherlands). In the present study, the minimum detection level for E. coli was 103 colonies per gram faeces. The antibiotic concentrations used (see Table 2) in the agar plates were based on NCCLS guidelines and modified (where appropriate) to make comparison with previous studies possible.4,5
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The prevalence of antibiotic resistance (%) was defined as the number of faecal samples with resistant E. coli divided by the total number of samples with detectable E. coli and multiplied by 100. The prevalence of resistance against amoxicillin, cefazolin, ciprofloxacin, co-amoxiclav, gentamicin, nalidixic acid, nitrofurantoin, oxytetracycline and trimethoprim was determined. The consumption of antibiotics during hospitalization in the three patient populations was expressed as the number of defined daily dosages (DDD) per 100 bed days. Statistical comparisons were carried out using the 2 test or Fishers exact test. P < 0.05 was considered significant.
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Results |
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The overall response of participation in the study was ±30%. The reason that patients did not want to participate was mainly because they were physically unable or had psychological reasons. Of the 400 patients, 268 were enrolled in the study; faecal samples were collected on admission, at time of discharge, and 1 month after discharge (azG = 83, azM = 94, azR = 91), and for 221 patients a faecal sample was also collected 6 months after discharge (azG = 59, azM = 80, azR = 82).
There was no marked variation between the three patient populations, for mean age (azG = 51, azM = 58, azR = 63), use of antibiotics (azG = 25%, azM = 30%, azR = 18%) and hospitalization (azG = 27%, azM = 26%, azR = 32%) in the 3 months before admission. Almost half of the azM patients were admitted for gastrointestinal surgery (47%), whereas azR patients were admitted most often for vascular surgery (49%) and azG patients for oncology-related surgery (52%). The majority of patients underwent surgery during hospitalization (azG = 99%, azM = 86%, azR = 98%). The median length of stay for the populations of azG, azR and azM was 6, 8 and 10 days, respectively.
Table 1 presents the consumption of antibiotics for systemic use during hospitalization. The percentages of patients receiving antibiotics in the patient populations of azM, azR and azG were 93%, 62% and 34%, whereas the percentages of patients receiving antimicrobial prophylaxis were 78%, 49% and 34%, respectively. In the azM population, co-amoxiclav was used for antimicrobial prophylaxis, and 41% also received co-amoxiclav for therapy. For the azR patients, the antibiotics used for therapy were diverse, whereas cefazolin with or without metronidazole was used exclusively for prophylaxis. The azG patients were most often prescribed ciprofloxacin for therapy (18%) and cefuroxime with or without metronidazole was used for prophylaxis (Table 1).
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Table 2 presents the prevalence of antibiotic resistance for the samples with detectable E. coli at the different time intervals. No significant differences in the prevalence of resistance were found between admission, time of discharge, and 1 and 6 months after discharge, both for the total population and the separate hospitals. One exception was the significant decrease in the prevalence of cefazolin-resistant E. coli from the azM patients between discharge (17%) and 6 months thereafter (6%). In addition, a similar decrease was found for the total patient population (P < 0.05). The azM patients showed a significantly higher prevalence of cefazolin resistance on admission, at time of discharge and 1 month after discharge compared with the azG patients and also at time of discharge for the azR patients (P < 0.05) (Table 2).
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Discussion |
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Selection pressure by antibiotics is considered the most important factor in the emergence of antibiotic resistance. The azM patients were mostly exposed to antibiotics. This high use of antibiotics can be explained by the fact that the majority of azM patients underwent (clean-) contaminated surgery, which because of higher infection risk is an indication for antimicrobial prophylaxis,6 whereas the majority of azR and azG patients underwent clean surgery (75% and 85%, respectively). However, the higher selection pressure in azM patients due to the use of co-amoxiclav did not seem to have any effect on the observed prevalence of co-amoxiclav or amoxicillin resistance. The patients that used antibiotics during hospitalization showed a significantly higher prevalence of cefazolin resistance at the time of discharge. One might speculate that the high use of co-amoxiclav induced the increase in cefazolin resistance observed at time of discharge. The use of cefazolin for prophylaxis in the azR patients did not seem to affect the prevalence of cefazolin resistance.
On surgical wards, antibiotic use is relatively low compared with other wards such as haematology or intensive care units. In addition, the average length of stay in these wards is usually longer and patients are often severely immunocompromised, which facilitates dissemination of and colonization by antibiotic-resistant bacteria. Studying antibiotic resistance in these hospital populations would have led perhaps to a more pronounced effect on the prevalence of antibiotic resistance.
In this study, hospitalization did not seem to have any substantial effect on the prevalence of antibiotic-resistant E. coli at the different time intervals. However, as our study population consisted of surgical patients with a relatively moderate antibiotic use, and the prevalence of antibiotic resistance was only analysed for faecal E. coli, further investigation should be encouraged, as the understanding of the interaction between different resistance reservoirs is important for directing future intervention studies.
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Acknowledgements |
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Footnotes |
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References |
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2 . Giamarellou, H. & Antoniadou, A. (1997). The effect of monitoring of antibiotic use on decreasing antibiotic resistance in the hospital. Ciba Foundation Symposium 207, 7686.[ISI][Medline]
3 . London, N., Nijsten, R., van den Bogaard, A. & Stobberingh, E. (1993). Antibiotic resistance of faecal Enterobacteriaceae isolated from healthy volunteers, a 15-week follow-up study. Journal of Antimicrobial Chemotherapy 32, 8391.[Abstract]
4 . Bruinsma, N., Filius, P. M. G., de Smet, P. A. G. M., Degener, J., Endtz, Ph., van den Bogaard, A. E. et al. (2002). Antibiotic usage and resistance in different regions of the Dutch community. Microbial Drug Resistance 8, 20914.[CrossRef][ISI][Medline]
5 . London, N., Nijsten, R., van den Bogaard, A. & Stobberingh, E. (1994). Carriage of antibiotic-resistant Escherichia coli by healthy volunteers during a 15-week period. Infection 22, 18792.[ISI][Medline]
6 . Van Kasteren, M. E. E., Gyssens, I. C., Kullberg, B. J., Bruining, H. A., Stobberingh, E. E. & Goris, R. J. A. (2000). Optimaliseren van het antibioticabeleid in Nederland. V. SWAB-richtlijnen voor perioperatieve antibiotische profylaxe. Nederlands Tijdschrift Geneeskunde 144, 204955.