BMJ 1999;319:1239-1240 ( 6 November )

General Practice

Antibiotic prescribing and antibiotic resistance in community practice: retrospective study, 1996-8

J T Magee, clinical scientist ^a,  Emma L Pritchard, medical student ^b,  Karen A Fitzgerald, pharmaceutical adviser ^c,  F D J Dunstan, senior lecturer ^d,  A J Howard, group director, PHLS Wales ^a,  on behalf of the Welsh Antibiotic Study Group.

^a Department of Medical Microbiology and Public Health Laboratory, University Hospital of Wales, Cardiff CF14 4XW, ^b University of Wales College of Medicine, Cardiff CF14 4XW, ^c Bro Taf Health Authority, Cardiff CF1 4TW, ^d Department of Medical Computing and Statistics, University of Wales College of Medicine

Correspondence to: A J Howard tony.howard{at}phls.wales.nhs.uk

We describe a retrospective survey of antibiotic prescribing in general practitioners' surgeries and resistance to antibiotics in Wales from March 1996 to April 1998.

	Methods and results

Top Methods and results Comment References

Data on the susceptibility to antibiotics of coliform organisms in routine urine samples taken by general practitioners for diagnosis of urinary tract infections were collected from the Bangor, Cardiff, and Rhyl Public Health Laboratories and the East Glamorgan, Prince Charles, and Wrexham Maelor Hospitals. Data on the prescribing practices of surgeries were obtained from the Welsh Prescription Pricing Service. Rates of prescribing (the number of prescriptions/1000 patients per year) and resistance rates (which excluded multiple isolates of organisms with the same susceptibility from the same patient) were calculated for each surgery. The use of broad spectrum penicillin formulations without a  lactamase inhibitor (such as ampicillin and amoxicillin) was estimated by subtracting the number of prescriptions for co-amoxiclav from the total number of prescriptions for all other broad spectrum penicillins. We use the term amoxicillin below to refer to these broad spectrum penicillins without a  lactamase inhibitor.

Resistance rates for surgeries which were based on fewer than 50 isolates were excluded, leaving data on about 30 000 isolates from 190 general practitioner surgeries serving about 1 200 000 patients. We sought to identify the effects of bias caused by the selective submission of urine samples by examining the relation between resistance rates and sampling (number of urine specimens/1000 registered patients) and the relation between positivity (number of coliform isolates/100 samples or 1000 registered patients) and prescribing or sampling.

The use of antibiotics and rates of resistance to antibiotics varied between surgeries; the correlation between the prescribing of an antibiotic and resistance to the same antibiotic was often significant (table). The correlation was also significant between the use of amoxicillin and resistance to trimethoprim and vice versa. Combined resistance to ampicillin and trimethoprim occurred in 21% (6782/32 532) of isolates and was significantly associated with the use of both trimethoprim and amoxicillin (P<0.001). The correlation between the use of amoxicillin and resistance to trimethoprim and vice versa was lost when strains exhibiting combined resistance to both agents were removed from the analysis.

View this table: [in this window] [in a new window]   P value and Spearman's correlation coefficient (95% confidence interval) for use of antibiotics and rate of antibiotic resistance (excluding repeat isolates) among general practitioner surgeries in Wales, 1996-8

There was no significant correlation between antibiotic use and the number of urine specimens submitted for testing per 1000 registered patients or the number of coliform isolates in urine samples per 1000 registered patients. The number of isolates per 1000 registered patients correlated linearly with the number of urine specimens submitted per 1000 registered patients (P=0.001, rs=0.9585).

	Comment

Top Methods and results Comment References

The results show that there is a correlation between antibiotic resistance in coliform organisms in urine samples and the use of antibiotics by a general practice. This is the first survey to suggest that geographically localised effects from antibiotic use occur in communities.

The dynamics of the emergence, spread, and maintenance of antibiotic resistance in populations are still unclear.¹ Much of the prescribing described here is likely to have been related to treatment of respiratory infections, and this may have been an important factor in determining the observed resistance. Resistance could be occurring through the prior selection of antibiotic resistant coliform organisms in the faecal flora² of patients presenting with urinary infections or by transmission of such organisms by others in the community.

Coselection of resistance to trimethoprim and ampicillin is explainable. Transmissible plasmids that code for combined resistance to ampicillin and trimethoprim are common in Escherichia coli³; therefore, selection pressure for resistance to one of these antibiotics is likely to select for resistance to the other.

The association between prescribing and resistance could have been caused by sampling bias if practices that had high rates of prescribing antibiotics were more selective in submitting samples for analysis, reserving testing for cases of treatment failure or complicated urological problems. In such cases it is likely that increased resistance would have been associated with lower rates of sampling. This was not observed. Few of the species of the coliform isolates were identified. Most were probably Escherichia coli, and it is unlikely that the small proportion of other coliform organisms (which often show broader resistance to antibiotics) would vary significantly between practices and be associated only with surgeries with high rates of prescribing. Other confounding variables may explain the observed correlations but it seems probable that the relations reflect a causal Darwinian association between prescribing and resistance.

These findings bring the debate on prescribing in the community from the national to the local level and provide preliminary evidence that practitioners may have to face the broader consequences of their antibiotic prescribing among their own patients.

	Acknowledgments

We thank the staff of the laboratories involved; the staff of the Prescription Pricing Authority; Drs Hefin Jones and Idris Humphreys, chairmen of the local medical committees, who gave permission for us to access the prescribing data; David Myles, University of Wales College of Medicine, for computing support; and David Livermore for his constructive comments.

Contributors: AJH conceived the original idea for the study, obtained approval for the collection of data, critically edited the paper, and gave final approval for it. AJH is guarantor for the study. JTM compiled and analysed the data, programmed the analysis macros, and drafted and edited the paper. ELP performed the pilot study, providing the impetus to proceed, and manually processed data that were invaluable in checking the validity of programs. KAF obtained the prescribing data and provided pharmaceutical advice. FDJD provided statistical guidance and checked the results. ELP, KAF, and FDJD participated in editing the paper.

	Footnotes

Funding: Public Health Laboratory Service.

Competing interests: None declared.

website extra: A complete list of the members of the study group appears on the BMJ's website www.bmj.com

	References

Top Methods and results Comment References

1.	Standing Medical Advisory Committee, Sub-Group on Antimicrobial Resistance. The path of least resistance. London: Stationery Office, 1998.
2.	London N, Nijsten R, Mertens P, van der Bogaard A, Sotobberingh E. Effect of antibiotic therapy on the antibiotic resistance of faecal Escherichia coli in patients attending general practitioners. J Antimicrob Chemother 1994; 34: 239-246[Abstract/Free Full Text].
3.	Amyes SGB. The success of plasmid-encoded resistance genes in clinical bacteriaan examination of plasmid-mediated ampicillin and trimethoprim resistance genes and their resistance mechanisms. J Med Microbiol 1989; 28: 73-83[Free Full Text].

(Accepted 19 July 1999)

---

© BMJ 1999
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

Relevant Article

Antibiotic resistance correlates with use of antibiotics by local practices
BMJ 1999 319: 0. [Full Text]

This article has been cited by other articles:

• Ochoa, T. J., Ruiz, J., Molina, M., Del Valle, L. J., Vargas, M., Gil, A. I., Ecker, L., Barletta, F., Hall, E., Cleary, T. G., Lanata, C. F. (2009). High Frequency of Antimicrobial Drug Resistance of Diarrheagenic Escherichia coli in Infants in Peru. Am J Trop Med Hyg 81: 296-301 [Abstract] [Full text]  
• Dong, L., Yan, H., Wang, D. (2008). Antibiotic prescribing patterns in village health clinics across 10 provinces of Western China. J Antimicrob Chemother 62: 410-415 [Abstract] [Full text]  
• Gabbay, V., Coffey, B. J., Babb, J. S., Meyer, L., Wachtel, C., Anam, S., Rabinovitz, B. (2008). Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcus: Comparison of Diagnosis and Treatment in the Community and at a Specialty Clinic. Pediatrics 122: 273-278 [Abstract] [Full text]  
• McNulty, C., Thomas, M., John, R., Lovering, A., Lewis, D., MacGowan, A. (2007). Problems of basing patient recruitment for primary care studies on routine laboratory submissions. J. Clin. Pathol. 60: 1290-1293 [Abstract] [Full text]  
• Fleming, D. M. (2007). The state of play in the battle against antimicrobial resistance: a general practitioner perspective. J Antimicrob Chemother 60: i49-i52 [Abstract] [Full text]  
• Reeves, D. (2007). The 2005 Garrod Lecture: The changing access of patients to antibiotics - for better or worse?. J Antimicrob Chemother 59: 333-341 [Abstract] [Full text]  
• McNulty, C. A. M., Richards, J., Livermore, D. M., Little, P., Charlett, A., Freeman, E., Harvey, I., Thomas, M. (2006). Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care. J Antimicrob Chemother 58: 1000-1008 [Abstract] [Full text]  
• Hay, A. D., Thomas, M., Montgomery, A., Wetherell, M., Lovering, A., McNulty, C., Lewis, D., Carron, B., Henderson, E., MacGowan, A. (2005). The relationship between primary care antibiotic prescribing and bacterial resistance in adults in the community: a controlled observational study using individual patient data. J Antimicrob Chemother 56: 146-153 [Abstract] [Full text]  
• Hummers-Pradier, E., Ohse, A. M., Koch, M., Heizmann, W. R, Kochen, M. M (2005). Management of urinary tract infections in female general practice patients. Fam Pract 22: 71-77 [Abstract] [Full text]  
• Duclos, C., Cartolano, G. L., Ghez, M., Venot, A. (2004). Structured Representation of the Pharmacodynamics Section of the Summary of Product Characteristics for Antibiotics: Application for Automated Extraction and Visualization of Their Antimicrobial Activity Spectra. J. Am. Med. Inform. Assoc. 11: 285-293 [Abstract] [Full text]  
• Donnan, P T, Wei, L, Steinke, D T, Phillips, G, Clarke, R, Noone, A, Sullivan, F M, MacDonald, T M, Davey, P G (2004). Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data. BMJ 328: 1297- [Abstract] [Full text]  
• Resi, D., Milandri, M., Moro, M. L., the Emilia Romagna Study Group on the Use of Antib, (2003). Antibiotic prescriptions in children. J Antimicrob Chemother 52: 282-286 [Abstract] [Full text]  
• Efstathiou, S. P., Pefanis, A. V., Tsioulos, D. I., Zacharos, I. D., Tsiakou, A. G., Mitromaras, A. G., Mastorantonakis, S. E., Kanavaki, S. N., Mountokalakis, T. D. (2003). Acute Pyelonephritis in Adults: Prediction of Mortality and Failure of Treatment. Arch Intern Med 163: 1206-1212 [Abstract] [Full text]  
• Gilbert, P., McBain, A. J. (2003). Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance. Clin. Microbiol. Rev. 16: 189-208 [Abstract] [Full text]  
• Metlay, J. P., Strom, B. L., Asch, D. A. (2003). Prior antimicrobial drug exposure: a risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections. J Antimicrob Chemother 51: 963-970 [Abstract] [Full text]  
• Mason, B. W., Howard, A. J., Magee, J. T. (2003). Fusidic acid resistance in community isolates of methicillin-susceptible Staphylococcus aureus and fusidic acid prescribing. J Antimicrob Chemother 51: 1033-1036 [Abstract] [Full text]  
• Fahey, T., Webb, E., Montgomery, A. A, Heyderman, R. S (2003). Clinical management of urinary tract infection in women: a prospective cohort study. Fam Pract 20: 1-6 [Abstract] [Full text]  
• Kahlmeter, G. (2003). An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO{middle dot}SENS Project. J Antimicrob Chemother 51: 69-76 [Abstract] [Full text]  
• Hillier, S. L., Magee, J. T., Howard, A. J., Palmer, S. R. (2002). How strong is the evidence that antibiotic use is a risk factor for antibiotic-resistant, community-acquired urinary tract infection?. J Antimicrob Chemother 50: 241-247 [Abstract] [Full text]  
• McIsaac, W. J., Low, D. E., Biringer, A., Pimlott, N., Evans, M., Glazier, R. (2002). The Impact of Empirical Management of Acute Cystitis on Unnecessary Antibiotic Use. Arch Intern Med 162: 600-605 [Abstract] [Full text]  
• Ball, P., Baquero, F., Cars, O., File, T., Garau, J., Klugman, K., Low, D. E., Rubinstein, E., Wise, R., Consensus Group on Resistance and Prescribing in R, T. (2002). Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence. J Antimicrob Chemother 49: 31-40 [Abstract] [Full text]  
• Lawrenson, R. A., Logie, J. W. (2001). Antibiotic failure in the treatment of urinary tract infections in young women. J Antimicrob Chemother 48: 895-901 [Abstract] [Full text]  
• Baerheim, A. (2001). Empirical treatment of uncomplicated cystitis. BMJ 323: 1197-1198 [Full text]  
• Priest, P., Yudkin, P., McNulty, C., Mant, D., Wise, R. (2001). Antibacterial prescribing and antibacterial resistance in English general practice: cross sectional study Commentary: antibiotic resistance is a dynamic process. BMJ 323: 1037-1041 [Abstract] [Full text]  
• Butler, C. C., Kinnersley, P., Prout, H., Rollnick, S., Edwards, A., Elwyn, G. (2001). Antibiotics and shared decision-making in primary care. J Antimicrob Chemother 48: 435-440 [Abstract] [Full text]  
• Solomon, D. H., Van Houten, L., Glynn, R. J., Baden, L., Curtis, K., Schrager, H., Avorn, J. (2001). Academic Detailing to Improve Use of Broad-Spectrum Antibiotics at an Academic Medical Center. Arch Intern Med 161: 1897-1902 [Abstract] [Full text]  
• Steinke, D. T., Seaton, R. A., Phillips, G., MacDonald, T. M., Davey, P. G. (2001). Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors. J Antimicrob Chemother 47: 781-787 [Abstract] [Full text]  
• Millar, M. R., Walsh, T. R., Linton, C. J., Zhang, S., Leeming, J. P., Bennett, P. M. (2001). Carriage of antibiotic-resistant bacteria by healthy children. J Antimicrob Chemother 47: 605-610 [Abstract] [Full text]  
• Howard, A. J., Magee, J. T., Fitzgerald, K. A., Dunstan, F. D. J. (2001). Factors associated with antibiotic resistance in coliform organisms from community urinary tract infection in Wales. J Antimicrob Chemother 47: 305-313 [Abstract] [Full text]  
• Millar, M. R., Russell, E., Karcher, A. M., Neville, L., Portia, O.-B. (2001). Prescribing quality is not synonymous with cost minimization for antibiotics. J Antimicrob Chemother 47: 367-368 [Full text]  
• STEELE, K, GORMLEY, G, WEBB, C H (2001). Management of adult lower respiratory tract infection in primary care. Thorax 56: 87-88 [Full text]  
• Livermore, D. M., Stephens, P., Weinberg, J., Johnson, A. P., Gifford, T., Northcott, D., James, D., George, R. C., Speller, D. C. E. (2000). Regional variation in ampicillin and trimethoprim resistance in Escherichia coli in England from 1990 to 1997, in relation to antibacterial prescribing. J Antimicrob Chemother 46: 411-422 [Abstract] [Full text]  
• McNulty, C. A. M., Kane, A., Foy, C. J. W., Sykes, J., Saunders, P., Cartwright, K. A. V. (2000). Primary care workshops can reduce and rationalize antibiotic prescribing. J Antimicrob Chemother 46: 493-499 [Abstract] [Full text]  

Rapid Responses:

Read all Rapid Responses

Addressing the issues arising from antibiotic prescribing

Alexander Williams
bmj.com, 16 Nov 1999 [Full text]

Response

P A Riley
bmj.com, 18 Nov 1999 [Full text]

Antibiotic prescribing and antibiotic resistance in the community

Evdokia Dardamissis
bmj.com, 3 Dec 1999 [Full text]

ANTIMICROBIAL RESISTANCE

Cameron T McGee
bmj.com, 16 Jan 2000 [Full text]

Online poll

Find out more>>