JAC Advance Access originally published online on April 9, 2008
Journal of Antimicrobial Chemotherapy 2008 62(2):410-415; doi:10.1093/jac/dkn153
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Original research |
Antibiotic prescribing patterns in village health clinics across 10 provinces of Western China
1 Department of Epidemiology and Health Statistics, School of Public Health, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China 2 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
* Corresponding author. Tel: +86-29-8265-5001; Fax: +86-29-8265-5387; E-mail: xjtu_yh.paper{at}yahoo.com.cn
Received 5 December 2007; returned 28 December 2007; revised 26 February 2008; accepted 12 March 2008
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Abstract |
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Objectives: To explore antibiotic prescribing patterns in rural areas across 10 provinces of Western China and to compare the patterns among these provinces.
Methods: About 20 125 prescriptions were collected from 680 primary health clinics in villages from 40 counties in 10 provinces of Western China. Percentage of prescriptions with antibiotics and number of antibiotics per 100 prescriptions were used as measurements of antibiotic utilization.
Results: The percentage of prescriptions with antibiotics was 48.43 (range: 41.12–57.47) in the study areas. There were 49 kinds of antibiotics prescribed in total, and 17 of them accounted for 90% of all usage. The number of antibiotics per 100 prescriptions was 54.62 (range: 43.78–69.56).
Conclusions: The frequency and proportion of prescribed antibiotics in the rural areas of Western China are higher compared with the developed countries, and the patterns of antibiotic prescription differ greatly among provinces. The findings have important policy implications for recommendations on the utilization of antibiotics in China.
Keywords: antibiotic prescriptions , pharmacoepidemiology , rural population
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Introduction |
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Antibiotics were once considered ‘miracle drugs’ and have been used for decades to effectively treat a variety of bacterial infections. Unfortunately, widespread use and misuse worldwide have led to the emergence of ‘super bugs’ and other drug-resistant bacteria.1–6 Unnecessary use of antibiotics has also given rise to an increased risk of side effects, high costs and effects requiring medical attention. The problem is particularly acute in China, where antibiotics are freely available over the counter.7 However, little research in antibiotic prescribing has been conducted in China, and particularly, the information on misuse of antibiotics in Chinese rural population is scarce. In this study, we aim to describe the quantity and pattern of antibiotic prescribing in village health clinics of Western China and to assess their regional differences among 10 provinces.
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Materials and methods |
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Study population and design
In this cross-sectional study, 40 counties from 10 provinces of Western China were included. These counties consisted of 748 townships and 10 170 villages. The area and population size of these 40 counties in the 10 provinces are shown in Table 1. The rural population accounted for 83.57% (range: 65.65% to 95.27%) of the total population. Considering the hierarchical structure of Chinese administrative districts and the imbalanced population distributions among different provinces, a 3-stage probability proportion to size sampling method was used in the study. Five townships were selected from each county by the following steps. First, we ordered all the townships in a county from smallest to largest according to the population size. Secondly, we calculated the accumulated population size. Thirdly, we calculated the sampling interval by dividing the total population of the county by 5. Suppose that the total population size is 202 000, the sample interval is 202 000/5 = 40 400. In the fourth step, a random number was determined by reading a serial number from a banknote of Renminbi (Chinese currency). The random number consisted of the last digits of this serial number but had the same length as that of the sampling interval. For example, if the serial number from Renminbi banknote is 98272809, then the random number is 72 809 since the sampling interval had five digits. Then, the first selection number was determined by taking the absolute value of difference between the random number and the sampling interval. Lastly, we looked up the township with the just accumulated population size, which contained the first selection number. That was the first township from this county to be included in this study. The second selection number was the first selection number plus the sampling interval, and thus, the second township was selected. In the same way, the third, the fourth and the fifth township were selected. Similarly, four villages were selected from each selected township. The sampling interval for village selection was calculated by dividing the total population size of a township by 4. Finally, 200 townships and 680 villages were selected from these 40 counties.
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The village health clinic in each selected village served as the data collection site. Data were collected at each village health clinic by investigators from Xi'an Jiaotong University College of Medicine from 23 June 2005 to 9 August 2005. The last 30 paper prescriptions written by village doctors up to 31 May 2005 were collected. Because there were no inpatients in village health clinics in rural Western China, all the 20 125 prescriptions collected in the study were for outpatients. Signed informed consent was obtained from the village doctors after this study was fully explained to them. The protocol was reviewed and approved by the Human Research Ethics Committee of the Xi'an Jiaotong University College of Medicine.
The percentage of prescriptions with one or more antibiotics, the number of antibiotics per prescription and the percentage of prescriptions with two or more antibiotics were determined. These measurements reflect antibiotic utilization from several different aspects. The percentage of prescriptions with antibiotics indicates the proportion of encounters who get antibiotics from village clinics. The number of antibiotics per prescription indicates how many antibiotics were used at a time. The percent of prescriptions with two or more antibiotics indicates the extent of antibiotic combination utilization.
Antibiotic classification in this study was based on the anatomical therapeutic chemical (ATC) classification system which is arranged in five levels. The ATC system is in general use for the classification of antibiotics.
The number of antibiotics of a class per 100 prescriptions (all prescriptions with or without antibiotics) served as an indicator of frequency of antibiotic utilization. The proportion of antibiotics belonging to the same class was expressed as the number of a certain class of antibiotics to the total number of prescribed antibiotics.
The diagnoses in prescriptions were classified according to the International Classification of Diseases 10th version (ICD-10).
The Kruskal–Wallis H-test and the Nemenyi test were used to compare the antibiotic use among the provinces, and 
2 approximation was used for the large numbers in the tests. The mean rank of each province which indicated the overall level of antibiotic prescribing in this area was derived from the Kruskal–Wallis test.
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Results |
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Data collection
Data from 680 of 800 villages and 20 125 of 24 000 prescriptions were analysed in this study. All the prescriptions collected were written in March, April and May. More than 80% of them were in May, and 
15% were in April. There were 120 villages that were excluded for the following reasons: 38 villages without village clinics, 55 villages without doctors, 11 villages without prescriptions, 15 villages where village doctors were not found and a township that had only 3 villages. About 11 427 (56.78%) patients were male and 8698 (43.22%) were female. Patients were aged from 1 month to 98 years and the age distribution is displayed in Figure 1. About 56.55% of the patients were 21–60 years of age and 21.40% were 0–10 years of age.
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Antibiotic prescription pattern
The 20 125 prescriptions were classified into four groups according to the number of antibiotics per prescription (Table 2). The percentage of prescriptions with antibiotics was 48.43 (range: 41.12–57.47). In detail, prescriptions with one antibiotic comprised 40.64% of all prescriptions, varying between 31.41% and 48.28%; those with two antibiotics represented 7.08% (range: 3.75% to 11.40%) of the total and 0.72% (range: 0.15% to 1.2%) were for prescriptions with more than two antibiotics. On average, village general practitioners in higher rank provinces such as Xinjiang, Sichuan, Guangxi, Chongqing and Gansu tended to prescribe more antibiotics per prescription than in lower ones.
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The Kruskal–Wallis H-test demonstrated that the overall difference in antibiotic number patterns was significant (
2 = 245.40, 
= 9, P < 0.001) among the 10 provinces. The Nemenyi test for the difference in antibiotic number patterns for all pairwise comparisons was used between provinces. Multiple comparisons among 10 provinces involved 45 pairs of provinces, and the difference was statistically significant (
= 0.05) in 17 pairs. Antibiotic number per 100 prescriptions is shown in Table 3. The total frequency was 54.62% (range: 43.78% to 69.56%) among the 10 provinces. According to the fourth level of ATC categories, 20 antibiotic groups were found in the present study, each antibiotic in the study having one ATC code on the fifth level, and according to this code, there were 49 classes of antibiotics in use. Variations in selection of antibiotics among the 10 provinces were broad, with the range being from 23 to 38 (Table 3). Third-generation cephalosporins appeared in six only. The main antibiotics were penicillins, cephalosporins and macrolides in each province, whereas the antibiotic proportions in each class were strikingly different. Penicillins were predominantly prescribed in all provinces except Xinjiang, where cephalosporins were more prevalent. More macrolides were prescribed than cephalosporins in eight provinces, whereas the opposite pattern was observed in Xinjiang and Ningxia. There were no clear patterns in utilization of other antibiotics such as quinolone antibacterials, aminoglycoside antibacterials, tetracyclines and sulphonamides in 10 provinces.
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Antibiotics were ranked by their frequency (Table 4). Seventeen antibiotics accounted for
90% of all antibiotics prescribed in the 20 125 prescriptions, and the other 32 antibiotics made up the remainder. The most frequently prescribed five antibiotics, which represented 53.45% of all antibiotic prescriptions, were amoxicillin, benzylpenicillin, norfloxacin, cefalexin and trimethoprim/sulfamethoxazole. Amoxicillin was the most prevalent, appearing 11.66 times per 100 prescriptions, and its proportion was 21.34% of all prescribed antibiotics.
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Although both the percentage of prescriptions with antibiotics and the number of antibiotics per 100 prescriptions expressed the extent of antibiotic utilization, they were not always consistent in terms of magnitude as shown in Tables 2 and 3. For example, Qinghai had a lower percentage of prescriptions with antibiotics than Ningxia (41.12% versus 44.92%, Table 2), whereas the former had larger number of antibiotics per 100 prescriptions than the latter (53.23% versus 49.83%, Table 3). The reason was that Qinghai had more prescriptions with two or more than two antibiotics than Ningxia (9.71% versus 6.56%, Table 2).
There were 248 diagnoses in the study and they were ranked by the frequency and displayed in Table 5. It is clear that the vast majority of diagnoses (45.71%) were upper respiratory tract infections and diagnoses in the first 16 commonly diagnostic categories accounted for 80% of all diagnoses.
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Discussion |
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Rural areas of Western China are the most underdeveloped areas in China, where the healthcare services are poor. Most of the villages in this study had no pharmacies and village health clinics were the main source of drug supplies. In the present study, more than one-half of the prescriptions were for upper respiratory tract infectious diseases or diarrhoeal diseases and more than half of the prescriptions for these diseases contained antibiotics. This study investigated antibiotic prescribing patterns using the number of antibiotics and the proportion of antibiotic prescription by the ATC category in the 10 provinces of Western China.
Prescriptions with antibiotics approximated one-half of all prescriptions from village clinics in rural areas of Western China. This figure varies around the world: 54.8% in Lagos, Nigeria, 67% in Hai Phong Province, Vietnam, 27.1% in a primary healthcare centre in Lebanon, 15.3% in the United States and 32% in Spain.8–12 It seems that antibiotics are more likely to be prescribed for patients in rural areas of Western China than in America and in European countries, but less likely than in other countries such as Vietnam and Nigeria.
Proportion of prescriptions with two or more antibiotics in the study was not high in comparison with other studies in Turkey and in Nigeria.8,13 The proportion increased with age, and this linear tendency was statistically significant (P < 0.001). The elderly had a greater tendency towards combination antibiotic utilization than younger patients. This is consistent with polypharmacy being seen more often in the elderly.
Number of antibiotic classes used in rural areas of Western China represented less than a quarter of antibiotics listed in J01 antibacterials for systemic use in ATC system. This is similar to the situation in Italy.14
Broad-spectrum penicillins were more prevalent than narrow-spectrum ones in this study. Excluding some Northern European countries, such as Sweden, Norway and Denmark, this is similar to most European countries.15–19 An obvious advantage of broad-spectrum antibiotics means least requirement for identification of the infecting pathogen in comparison with narrow-spectrum antibiotics before treatment. Pathogen identification is difficult because of the remoteness of village clinics in Chinese rural areas. This could explain why broad-spectrum antibiotics were more prevalent than narrow-spectrum antibiotics. The patient's normal flora will be affected by them, and antibiotic resistance might be accelerated.20 Third-generation cephalosporins were used mostly for inpatients with hospital-acquired infections because of their broad spectrum and activity. Third-generation cephalosporins for outpatients should be used sparingly because unwarranted utilization may result in antibiotic resistance and side effects. Less utilization of third-generation cephalosporins leads to a decrease in the acquisition of extended-spectrum β-lactamase-producing infection.21–24 Although the utilization of third-generation cephalosporins was negligible in most provinces, it was exceptional in Xinjiang and noticeable in Qinghai. In Chinese rural areas, village clinics have no facilities to treat serious infectious diseases systemically. The utilization of these drugs in village clinics is probably unwarranted.
The importance of this study is that it is the largest study of prescribing patterns in Chinese rural areas. Data collection sites were scattered in 151 548 km2. Original paper prescriptions collected from village clinics guaranteed the authenticity of the findings. The limitation of this study is that it is a clinic-based study, in which the self-medication has not been taken into consideration. Consequently, the true frequency and proportion of antibiotic use may have been underestimated. Data from prescriptions did not include information on the patients' recovery, and the outcome of drug utilization could not be analysed in the present study. As the prevalence of infectious diseases varies with the seasons, antibiotic prescribing and utilization varies accordingly. Data collected in May will affect the generalizability to other seasons especially to winter because the incidence of upper respiratory tract infections is particularly high during winter.
In conclusion, this study described antibiotic number patterns and antibiotic category patterns in village health clinics across 10 provinces of Western China. The results demonstrate that antibiotics are used frequently and that antibiotic choice mainly comprises 17 antibiotics in common use. Antibiotic prescribing patterns have a different characterization in each province. Although causal inferences cannot be made in the present study, there are some underlying public beliefs that may explain the high level of antibiotic use such as doctors' (or patients’) poor awareness of the dire consequences of overuse of antibiotics, irrational use of antibiotics due to financial incentives and profit-driven prescribing behaviours and no effective supervisory measures for antibiotic utilization. Further studies should be conducted to investigate reasons for overuse of antibiotics in Western China and how to reduce the high-use rate.
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Funding |
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Financial support came from the Chinese Ministry of Health (MOH) and the United Nations Children's Fund (UNICEF).
Author contributions: L. D. designed the prescription study, collected the data, conducted the data analysis and prepared the manuscript; H. Y. contributed to the design and analysis of the study and the preparation of the manuscript; and D. W. assisted with the data analysis and reviewed the manuscript.
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Transparency declarations |
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None to declare.
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Acknowledgements |
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We would like to thank all of the general practitioners who participated in this study. We also greatly appreciate all investigators' efforts regarding data collection.
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References |
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