Tropical Medicine and International Health
doi:10.1111/tmi.12327
volume 19 no 7 pp 761–768 july 2014
Antibiotic prescribing practice for acute, uncomplicated respiratory tract infections in primary care settings in New Delhi, India Anita Kotwani1 and Kathleen Holloway2 1 Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi, India 2 Essential Drugs and Other Medicines, WHO, Regional Office for South East Asia, New Delhi, India
Abstract
objective To obtain information on prescribing rates and choice of antibiotics for acute, uncomplicated respiratory tract infections (RTIs) in the community. methods Antibiotic use in acute, uncomplicated RTIs consisting of common cold/sore throat/cough for not more than five days was surveyed in the community (December 2007–November 2008) using patient exit interviews at public and private facilities from four localities in New Delhi. Data were collected from 10 public sector facilities and 20 private clinics over one year. The percentage of acute, uncomplicated RTIs patients receiving antibiotics in general and using the Anatomical Therapeutic Chemical classification and the Defined Daily Dose (ATS/DDD) were analysed. results At public and private facilities, 45% (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed at least one antibiotic, respectively. The main antibiotic class calculated as percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI patients at private clinics was cephalosporins, J01DA (39%), followed by fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA (15%). Newer members from each class were prescribed; older antibiotics such as co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the main class of antibiotic prescribed was penicillins (31%), followed by macrolides (25%), fluoroquinolones (20%) and cephalosporins (10%). conclusions Study clearly shows overuse and inappropriate choice of antibiotics for the treatment of acute, uncomplicated RTIs which are mainly due to virus and do not require antibiotic treatment. Results of the study warrant interventional strategies to promote rational use of antibiotics to decrease the overgrowing threat of antibiotic resistance. keywords antibiotics prescribing, antibiotic resistance, community pharmacists, primary care, rational use of antibiotics, upper respiratory tract infections
Introduction Globally, antibiotic resistance is being recognised as a major healthcare issue; local, national and international efforts are needed to counteract its emergence. Antibiotic use is considered as a key contributor for the increase and spread of antibiotic resistance (Albrich et al. 2004). A major concern is the inappropriate use of antibiotics for non-bacterial infections and for self-limiting clinical conditions. Antibiotic usage in primary healthcare settings is high, and consumption of antibiotics for respiratory tract infections is the most common indication as documented for the developed world (Goossens et al. 2005). Upper respiratory tract infections (URTIs) are the most commonly treated acute problems in primary care
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(Thamlikitkul & Apisitwittaya 2004; Francis et al. 2009), with the majority of infections of viral origin (Mono 2002; Van Gageldonk-Lafeber et al. 2005). However, data from developing countries for antibiotic use for URTIs are scarce, and surveillance of antibiotic use in the community is not in place. Data and pattern on antibiotic use and resistance are prerequisite for development, implementation and assessment of antibiotic guidelines and for local and national prescribing policies (MalhotraKumar et al. 2004; Goossens et al. 2007). Upper respiratory tract infections or nasopharyngitis and colds are conditions that are most likely caused by viruses (Nyquist et al. 1998; Snow et al. 2001) and therefore do not require antibiotics (O’Brien et al. 1998; Rosentein et al. 1998; Avorn & Solomon 2000). 761
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Gadomski (1993) performed a meta-analysis addressing the treatment of non-specific URTIs and found that antibiotics neither shortened the length of upper respiratory illness nor prevented the development of pneumonia. The Centers for Disease Control (CDC) and the American Academy of Pediatrics (AAP) both advocate the same principle regarding the common cold that the use of antimicrobial agents should be avoided (Jacobs 2000). Children treated unnecessarily are at high risk for developing penicillin-resistant Streptococcus pneumonia (PRSP) (Tomaz 1994; Frick et al. 1998). Unfortunately, URTIs are common conditions for which the misuse of antibiotics is common and is reported from different parts of the world (Evans et al. 2005; Van den Broek d’Obrenan et al. 2014). Understanding the extent and pattern of antibiotics use for acute URTIs in the community is important for developing a regional intervention programme to promote the rational use of antibiotics and thus limits the spread of antimicrobial resistance for developing country where a surveillance system and antibiotic policy are generally not developed. Hence, this study was conducted in New Delhi, India. The primary aims of this study were (i) to find out the percentage of antibiotic prescriptions by primary healthcare providers in public and private sectors with acute, uncomplicated RTIs, the majority of which will be URTI, and (ii) to determine the pattern of antibiotic choice in public and private sectors for these conditions in New Delhi, India. As the diagnosis is generally not recorded on prescriptions, diagnosis had to be ascertained by asking patients about their symptoms. This made it difficult to separate URTI from LRTI. However, effort was made to focus on symptoms of acute, uncomplicated RTIs like common cold/sore throat and acute cough, the majority of which will be viral URTI and self-limiting. Findings about the use of antibiotics in such conditions will give some indication of inappropriate use of antibiotics and would be valuable in developing strategies to improve primary care doctors’ prescribing routine. This study was conducted from December 2007 to November 2008. Methods This study was part of a larger study on surveillance of antibiotic use and resistance in the community, and data were collected from four residential localities (municipal wards) of New Delhi, India. The four areas were as follows: Rajinder Nagar, Patel Nagar, Karol Bagh and Rajouri Garden. To get a complete picture of antibiotic use in the community for acute, uncomplicated RTIs, both public and 762
private sector facilities were surveyed. In the public sector, all eight dispensaries (primary healthcare facility) and two small hospitals (secondary care level) under Government of National Capital Territory of Delhi (GNCT, Delhi) in the study area were enrolled. At public facilities, prescribed medicines are provided free to the population if those medicines are available in the facility. Twenty private sector general practitioners and specialists willing to cooperate for the study, practising in the chosen areas, including four paediatricians, three physicians and 13 general practitioners (GPs) were included from the private sector. At private facilities, patients must pay for medicines. In the absence of community-based databases on antibiotic use, absence of disease-code classification, frequent absence of facility-based patient notes and doctors often not writing the diagnosis on the prescription, a method recently established for the surveillance of antibiotic use at New Delhi by conducting ‘exit interviews’ of the patients (Kotwani et al. 2009; WHO 2009a,b; Kotwani & Holloway 2011) was used. Patients were asked about symptoms which generally represent uncomplicated respiratory infections and are self-limiting. Data on antibiotic use were collected by trained data collectors (pharmacists) who conducted exit interviews of patients leaving the facility (Kotwani & Holloway 2011). Data collectors visited each public facility twice every month and private clinics thrice every month to collect the data. Data were collected from five private practitioners per month; the practitioners being randomly chosen every month were from a pool of 20 practitioners enrolled for the study. All the patients coming out from the prescriber’s office were asked whether they had common cold/sore throat/cough for the last 1–5 days and no persistent cough for more than five days. Data collectors also asked patients whether they had mentioned these same symptoms (common cold/sore throat/cough for the last 1–5 days) to the prescriber and whether the prescription they had received was for the same symptoms. Any patient with the above-mentioned symptoms was labelled as having acute, uncomplicated RTI and was enrolled for exit interview, and his/her prescription was monitored. Other patients who were classified as having severe diseases, for example cough for more than 5 days, a written diagnosis of pneumonia or otitis media in children, were excluded from the study. A pre-designed proforma was used to collect data regarding the name, dose and duration of antibiotic prescribed. Data collectors’ schedules were randomly prepared for the day and time (1 h) of visits every month for data collection.
© 2014 John Wiley & Sons Ltd
Tropical Medicine and International Health
volume 19 no 7 pp 761–768 july 2014
A. Kotwani & K. Holloway Antibiotic prescription practices in New Delhi
Antibiotic use was measured in terms of the percentage of acute, uncomplicated RTI patients receiving an antibiotic. To estimate this, the numerator was the number of acute, uncomplicated RTI patients receiving an antibiotic and the denominator was the total number of acute, uncomplicated RTI patients, whether or not they received antibiotics – both recorded during each facility visit for the time that the data collectors were in the facility. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were also assigned to the data (WHO 2008) to examine in detail the types of antibiotic prescribed. Prescribing patterns for various antibiotics in public and private clinics were analysed, and the consumption of each antibiotic was expressed as percentage of total number of DDDs/ 1000 acute, uncomplicated RTI patients attending all the public or private facilities. All data were entered into software developed in Visual Basic, SQL Server and Crystal Reports. The same software was used to analyse the data. Ethical approval for the study was obtained from Vallabhbhai Patel Chest Institute, University of Delhi, India, and also from WHO’s Ethics Review Committee.
Informed consent was obtained from all participants and facilities involved in the study. Results A total of 1646 acute, uncomplicated RTI patients from public facilities and a total of 457 acute, uncomplicated RTI patients from private clinics were studied. No clear seasonal variation in number of acute, uncomplicated RTI patients was observed at both public and private facilities. Percentage of prescriptions with antibiotics for acute, uncomplicated RTIs Table 1 shows the percentage of patients who were prescribed various antibiotics. At public facilities, 45% of acute URTI patients were prescribed at least one antibiotic. Subgroup analysis for two secondary care level study hospitals showed that 44% of acute, uncomplicated RTI patients were given antibiotics (Table 1). Doctors at both types of public facility, that is, dispensaries (primary healthcare facilities) and secondary level hospitals (30
Table 1 Percentage of prescriptions with various antibiotics in acute, uncomplicated respiratory tract infections in public sector and private clinics (December 2007–November 2008) Total no. of patients
Prescriptions with antibiotics
% Prescriptions with antibiotics
% Distribution of various antibiotics used
Public sector (hospitals + dispensaries)
1646
746
45.3
2
Public sector (hospitals)
294
131
44.5
3
Private clinics
457
259 * 4 patients received 2 antibiotics
56.7
4
Private clinics (paediatrics)
138
84* 3 patients received 2 antibiotics
60.9
Macrolides (29.3) Penicillins (26.3) Cephalosporins (16.2) Fluoroquinolones (13.1) Co-trimoxazole (9.4) Tetracycline (5.4) Nalidixic acid (0.13) Aminoglycosides (0.13) Penicillins (30.5) Macrolides (24.4) Cephalosporins (19.8) Fluoroquinolones (19.1) Co-trimoxazole (12.2) Tetracycline (3.1) Cephalosporins (40.0) Fluoroquinolones (21.7) Penicillins (19.7) Macrolides (16.3) Tetracycline (1.9) Co-trimoxazole (0.4) Cephalosporins (49.4) Penicillins (20.7) Fluoroquinolones (15) Macrolides (13.8) Co-trimoxazole (1.1)
No.
Sector
1
© 2014 John Wiley & Sons Ltd
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A. Kotwani & K. Holloway Antibiotic prescription practices in New Delhi
and 50 bedded), prescribed antibiotics in a similar fashion. The highest consumption was for penicillins (J01C) and macrolides (J01FA), followed by cephalosporins (J01DA), fluoroquinolones (J01MA), co-trimoxazole (J01EF01) and tetracyclines (J01A). At private clinics, overall 57% of patients were prescribed any antibiotic for the treatment of acute, uncomplicated RTIs. On subgroup analysis for private clinics, the paediatricians prescribed antibiotics to 61% of children with acute, uncomplicated RTIs (Table 1). Both general physicians (GPs) and paediatricians mainly prescribed cephalosporins, followed by fluoroquinolones, penicillins and macrolides. The use of older antibiotics, such as co-trimoxazole or tetracyclines, was minimal (Table 1). Antibiotic prescription pattern in terms of DDDs for acute, uncomplicated RTIs Table 2 shows the number of DDDs for each class of antibiotics prescribed as a percentage of total DDDs for all antibiotics prescribed/1000 patients of acute, uncomplicated RTIs at public and private facilities surveyed. In the public sector, consumption in terms of DDDs shows that amoxicillin, ofloxacin and roxithromycin were the most commonly dispensed antibiotics for acute, uncomplicated RTIs. A few patients were also given older antibiotics such as erythromycin, doxycycline, ampicillin, cephalexin, cloxacillin, ciprofloxacin and tetracycline and relatively newer antibiotics such as amoxicillin+clavulanic acid and cefuroxime. In the private sector, consumption in terms of DDDs shows that newer antibiotics such as cefuroxime, cefpodoxime, cefixime and cefixime+clavulanic acid, levofloxacin, ofloxacin and roxithromycin were the most commonly prescribed antibiotics for acute, uncomplicated RTIs (Table 2). Older antibiotics were not generally used. Discussion Our study revealed that antibiotic prescriptions for acute, uncomplicated RTIs were common in primary care settings, more so in the private sector (57%) than in the public sector (45%). We focused on acute, uncomplicated RTI, most of which will have been viral URTI. It is unlikely that 40% or more of such patients would have had lower RTI requiring antibiotics, so the proportion of patients prescribed antibiotics would appear to be high. Other studies have also described antibiotic prescribing for non-specific RTI diagnosis. In primary care settings in the Netherlands (Van den Broek d’Obrenan et al. 2014), 764
Table 2 Pattern of antibiotic use for acute, uncomplicated respiratory tract infections in private and public facilities surveyed in Delhi, India (December 2007–November 2008)
Antibiotic name Cephalosporins J01DA Cefuroxime Cefpodoxime proxetil Cephalexin Cefixime Cefixime + clavulanic acid Cefaclor Others Fluoroquinolones J01MA Levofloxacin Ofloxacin Ciprofloxacin Norfloxacin Penicillins J01C Amoxicillin+clavulanic acid Amoxicillin Amoxicillin+cloxacillin Ampicillin Cloxacillin Macrolides J01FA Roxithromycin Azithromycin Erythromycin Tetracycline J01A Doxycycline Tetracycline Demeclocycline Combinations of sulphonamide with Trimethoprim (J01EE) Co-trimoxazole Total
Private clinics% of total DDDs of antibiotic prescribed to RTI patients 39.1 11.9 8.6 0.6 8.5 8.2 0.4 0.9 23.6 12.7 8.7 2.2 – 19.1 14.0 3.0 2.1 – 15.5 11.4 4.0 0.1 2.7 2.7
0.03
0.03 100
Public sector% of total DDDs for antibiotic prescribed to RTI prescribed 10.4 6.7 – 3.7 – – – 19.7 – 15.6 3.7 0.4 31.0 7.5 15.9 0.2 4.4 3.0 24.6 14.7 – 9.9 9.5 7.1 2.3 0.05 4.8
4.8 100
overall antibiotics were prescribed in approximately 25% of infectious disease episodes – amongst respiratory infections, for acute upper RTI approximately 20% and for cough approximately 16% of episodes. In primary care settings in Ireland (Murphy et al. 2012), there was considerable antibiotic prescribing for conditions not included in the guidelines such as URTI (33.1%), cough (35.8%) and sore throat (53.1%). In Poland, more than half of patients (54.2%) with a common cold were treated with an antibiotic (Panasiuk et al. 2010). Comparison with these data clearly shows that the percentage of patients who receive antibiotics for acute, uncomplicated RTIs in the present study at primary care was high. A
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Tropical Medicine and International Health
volume 19 no 7 pp 761–768 july 2014
A. Kotwani & K. Holloway Antibiotic prescription practices in New Delhi
WHO review of studies showed high antibiotic use for URTIs globally and in the Asia (WHO 2009a,b). The other important finding was the choice of antibiotic prescribed for these acute and uncomplicated symptoms such as common cold or sore throat or cough. In India, we do not have national or regional well-recognised official guidelines for the treatment of common diseases and infections for primary care settings. Moreover, the prescriptions in the private sector are not officially regulated. However, the Government of National Capital Territory of Delhi (GNCT) has an essential medicine list (EML), and this EML is separate for primary care and tertiary care hospitals. Procurement is supposed to be based on EML, and doctors are supposed to prescribe from it. The EML 2007 applicable at the time of the study for primary care comprised the following antibiotics: benzathine penicillin and procaine penicillin (powder for injection), amoxicillin, ampicillin, cloxacillin, ciprofloxacin, norfloxacin, nalidixic acid, erythromycin, roxithromycin, sulphamethoxazole + trimethoprim and doxycycline. Cephalexin was mentioned for restricted use only. These antibiotics are usually first-line or second-line choice for common infections and should be prescribed at primary care. The survey revealed that all antibiotics on the list of Delhi state EML, even those which were supposed to be reserve antibiotics for hospitals, such as third-generation cephalosporins (e.g. cefuroxime) and fluoroquinolones (e.g. levofloxacin) and amoxicillin+clavulanic acid, were available and used in dispensaries (primary healthcare facilities) as found in earlier surveys conducted in Delhi State (Kotwani & Holloway 2011, 2013; Kotwani et al. 2012). Thus, public procurement and distribution did not appear to be following the EML. At private clinics, where no official guidelines or EML is implemented, the pattern of antibiotic use was different. In India, around 80% of the population rely on private health care (Creese et al. 2004). The present survey revealed that second- and third-generation cephalosporins and other antibiotics such as levofloxacin, ofloxacin, amoxicillin+clavulanic acid and roxithromycin were prescribed for acute, uncomplicated RTIs. First-generation or first-line antibiotics such as co-trimoxazole, ampicillin, amoxicillin and erythromycin were rarely prescribed in private clinics. The above-mentioned three studies from the Netherlands, Ireland and Poland have shown a different pattern of antibiotic use in primary care for RTIs. In the Netherlands (Van den Broek d’Obrenan et al. 2014) for all respiratory infections, tetracyclines and amoxicillin accounted for about 65% of prescriptions and the prescription of macrolides and amoxicillin/clavulanate was about 14% and 10%, respectively. In Ireland (Murphy
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et al. 2012) for tonsillitis, 43% patients were prescribed phenoxypenicillin, which is the first-line antibiotic, and 20% amoxicillin and 25% co-amoxiclav, which are second-line antibiotics according to Irish national guidelines for the treatment of tonsillitis. In Poland (Panasiuk et al. 2010), high percentage of amoxicillin use for common cold, pharyngitis, tonsillitis and URTI of multiple or unspecified sites was reported. All these studies reported either minimal or no use of second- and third-generation cephalosporins or fluoroquinolone for common cold, pharyngitis, sinusitis and cough. In comparison with these studies, our survey showed that not only high antibiotic was high but also the choice of antibiotic for the treatment of acute, uncomplicated RTIs was also inappropriate. A qualitative study conducted with prescribers of both public and private sector facilities of the same municipal wards of Delhi where this study was conducted (Kotwani et al. 2010) revealed that private practitioners’ first important reason for prescribing antibiotic is financial consideration to not lose the patient to another doctor who will prescribe an antibiotic. The various other reasons doctors put forth for prescribing antibiotics were: diagnostic uncertainty whether infection is bacterial or viral; they perceive expectation for antibiotic prescription from patients; and to satisfy the patient by giving something more than just paracetamol. Doctors from public sector facilities mentioned that because of patient overcrowding, they do not have enough time to explain to the patients that antibiotics are not needed. These findings indicate that antibiotics are misused by many doctors for the treatment of acute, uncomplicated RTIs either due to financial gain and ignorance or due to various other perceived pressures. Similar behaviour and findings for doctors have been observed by other researchers (Van Driel et al. 2006). Other studies report that only a small proportion of patients explicitly expect a prescription, and even if they do, their primary concern is to find symptomatic relief (Altiner et al. 2004; Van Driel et al. 2006); patients were satisfied with careful examination and reassurance, irrespective of whether they received an antibiotic or not (Welschen et al. 2004; van Duijn et al. 2007; Fischer et al. 2008). Similar studies with respect to patients’ concerns, beliefs and satisfaction are urgently needed in developing countries. A qualitative study conducted by Kotwani et al. (2012) for retail pharmacists in these same residential areas of Delhi revealed that pharmacists mimic the prescription of neighbourhood general practitioners and they themselves prescribe and dispense antibiotics for one or two days for acute, uncomplicated RTIs. Therefore, it is very important that doctors prescribe antibiotics rationally, as their prescription is copied 765
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by others who are actually not legally entitled to prescribe antibiotics. Surveillance of antibiotic use in these same localities in New Delhi has shown a high use of fluoroquinolones and markedly increasing use of cephalosporins from 2004 to 2008 (Kotwani & Holloway 2011). The sales data indicate that overall units of antibiotic sold in India between 2005 and 2009 increased by about 40%. Increased sales of cephalosporins were particularly striking, increasing by 60% over that five-year period (Ganguly et al. 2011). This increase in use of cephalosporins is worrying from the prospective of increasing resistance to them. Our study also indicates the increasing use of cephalosporins in acute, uncomplicated RTIs in the private sector. Irrational use of cephalosporins in these communities is resulting in resistance observed in E. coli (Wattal et al. 2009), and the continuous overuse will increase the antimicrobial resistance. Growing antimicrobial resistance has become a worldwide health threat, and it is worrisome because of the dearth of new antibiotics being developed. The need for prompt action by all countries is urgently required to avert this developing global crisis. Surveillance of antibiotic use is one of the strategies to guide control of antibiotic overuse or misuse. Based on the country- or regionspecific data on pattern of antibiotic use, policy and guidelines for rational use of antibiotics should be prepared and implemented strictly. Quality assurance programmes and public campaigns have been developed and launched in Europe to improve the use of antibiotics in primary care (Welschen et al. 2004; Goossens et al., 2006; MacReady 2009). The positive effects reported with these projects suggest that their implementation in other countries with high antibiotic prescribing may be effective. In India, there is an urgent need to develop and implement treatment guidelines at primary care settings for rational use of antibiotics. The strength of this study is that it clearly shows that it is possible to collect useful data for antibiotic use in both public and private sector facilities, at the individual patient level in resource-constrained settings where a database is not available. This is one of the few studies conducted in India that have shown prescribing pattern of antibiotics for the treatment of acute, uncomplicated respiratory tract infections in both public and private sectors. Findings of this study can be useful for conducting intervention studies to improve rational use of antibiotics in acute RTIs. The study has some inherent weaknesses. Firstly, it was conducted in four residential localities of one urban area, so generalisation should be done with caution for the rest of Delhi and cannot be done for other areas of India. Secondly, the presence of data 766
collectors may have changed the prescribing habits of doctors at private clinics. Doctors may have prescribed fewer antibiotics than normally. In public facilities, the bias introduced into doctors’ prescribing may have been less as the data collectors were in the pharmacy area and doctors were not always aware which day and time data collectors were visiting. Misclassification as to whether patients were suffering from lower or upper respiratory tract infection may have occurred, but lack of recorded information on diagnosis meant that a patient interview was the only way to identify cases of acute, uncomplicated RTI. Nevertheless, care was taken to exclude as far as possible cases of RTI that may have needed antibiotics, and it is likely that there were only a small proportion of such cases. Conclusions and recommendations This study shows a high use of antibiotics by primary care doctors for the treatment of acute, uncomplicated respiratory tract infections, most of which will be self-limiting viral URTI. Choice of antibiotic was more inappropriate in private clinics, where cefuroxime, cefpodoxime proxetil, cefixime+clavulanic acid and amoxicillin+clavulanic acid were the main antibiotics prescribed. Standard treatment guidelines for the treatment of respiratory tract infections need to be urgently developed and strictly implemented in both public and private sectors in India. Acknowledgements We thank all the participating doctors, hospital in charge, Directorate Medical Services, Government of NCT, Delhi, and patients for their cooperation and support during the study. The project was funded by WHO.
References Albrich WC, Monnet DL & Harbarth S (2004) Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes. Emerging Infectious Disease 10, 514– 517. Altiner A, Knauf A, Moebes J, Sielk M & Wilm S (2004) Acute cough: a qualitative analysis of how GPs manage the consultation when patients explicitly or implicitly expect antibiotic prescriptions. Family Practice 21, 500–506. Avorn J & Solomon D (2000) Cultural and economic factors that (mis)shape antibiotic use: the nonpharmacologic basis of therapeutics. Annals of Internal Medicine 133, 128–135. Creese A, Kotwani A, Kutzin J. & Pillay A (2004) Evaluating pharmaceuticals for health policy in low and middle income country settings. In: Evaluating pharmaceuticals for health
© 2014 John Wiley & Sons Ltd
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volume 19 no 7 pp 761–768 july 2014
A. Kotwani & K. Holloway Antibiotic prescription practices in New Delhi
policy and reimbursement (eds N Freemantle & S Hill) Blackwell Publishing, BMJ Books and WHO, Massachusetts, pp. 227–243. van Duijn HJ, Kuyvenhoven MM, Schellevis FG & Verheij TJM (2007) Illness behaviour and antibiotic prescription in patients with respiratory tract symptoms. British Journal of General Practice 57, 561–568. Essential Medicine List (2007) Government of NCT Delhi. http://www.scribd.com/doc/12401543/Drug-list Evans CT, Smith B, Parada JP, Kurich JE & Weaver FM (2005) Trends in antibiotic prescribing for acute respiratory infections in veterans with spinal cord injury and disorder. Journal of Antimicrobial Chemotherapy 55, 1045–1049. Fischer T, Fischer S, Himmel W, Kochen MM & Hummers PE (2008) Family practitioners’ diagnostic decision-making processes regarding patients with respiratory tract infections: an observational study. Medical Decision Making 28, 810–818. Francis NA, Butler CC, Hood K, Simpson S, Wood F & Nuttal J (2009) Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster-randomised controlled trial. British Medical Journal 339b, 2885. Frick PA, Black DJ, Duchin JS, Deliganis S, McKee WM & Fritsche TR (1998) Prevalence of antimicrobial drug-resistant Streptococcus pneumoniae in Washington State. Western Journal of Medicine 169, 364–369. Gadomski AM (1993) Potential interventions for preventing pneumonia among young children:lack of effect of antibiotic treatment for respiratory infections. The Pediatric Infectious Disease Journal 12, 115–120. Ganguly NK, Arora NK, Chandy SJ et al. (2011) Rationalizing antibiotic use to limit antibiotic resistance in India. Indian Journal of Medical Research 134, 281–294. Goossens H, Guillemot D, Ferech M et al. (2006) National campaigns to improve antibiotic use. European Journal of Clinical Pharmacology 62, 373–379. Goossens H, Ferech R, Stichele RV & Elseviers M (2005) Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365, 579–587. Goossens H, Ferech M, Coenen S & Stephens P (2007) European surveillance of antimicrobial consumption project group. Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries. Clinical Infectious Disease 44, 1091–1095. Jacobs RF (2000) Judicious use of antibiotics for common pediatric respiratory infections. Pediatric Infectious Diseases 19, 938–940. Kotwani A & Holloway K (2011) Trends in antibiotic use among outpatients in New Delhi, India. BMC Infectious Diseases 11, 99. Kotwani A & Holloway K (2013) Access to antibiotics in New Delhi, India: implications for antibiotic policy. Journal of Pharmaceutical Policy and Practice 6, 6. Kotwani A, Holloway K & Chaudhury RR (2009) Methodology for surveillance of antimicrobials use among out-patient in Delhi. Indian Journal of Medical Research 129, 555–560.
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Kotwani A, Wattal C, Katewa S, Joshi PC & Holloway K (2010) Antibiotic use in the community: what factors influence primary care physicians to prescribe antibiotics in Delhi, India? Family Practice 27, 684–690. Kotwani A, Wattal C, Katewa S, Joshi PC & Holloway K (2012) Irrational use of antibiotics and role of pharmacists: an insight from a qualitative study in New Delhi, India. Journal of Clinical Pharmacy and Therapeutics 37, 308–312. MacReady N (2009) French campaign reduces antibiotic prescriptions. The Lancet Infectious Diseases 9, 469. Malhotra-Kumar S, lammens C, Piessens J & Goossens H (2004) Oropharyngeal carriage of macrolide-resistant viridans group streptococci : a prevalence study among healthy adults in Belgium. Journal of Antimicrobial Chemotherapy 53, 271–276. Mono AS (2002) Epidemiology of viral respiratory infections. American Journal of Medicine 112(suppl 6A), 4S–12S. Murphy M, Bradley CP & Byone S (2012) Antibiotic prescribing in primary care, adherence to guidelines and unnecessary prescribing – an Irish perspective. BMC Family Practice 13, 43. Nyquist AC, Gonzales R & Steiner Sande MA (1998) Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. Journal of the American Medical Association 279, 855–877. O’Brien KL, Dowell SF & Schwartz B (1998) Acute sinusitisprinciples of judicious use of antimicrobial agents. Pediatrics 101, 174–176. Panasiuk L, Lukas W, Paprzycki P, Verheij T, Godycki-Cwirko M & Chlabicz S (2010) Antibiotics in the treatment of upper respiratory tract infections in Poland. Is there any improvement? Journal of Clinical Pharmacy & Therapeutics 35, 665– 669. Rosentein N, Philips WR, Gerber MA, Marcy SM, Schwartz B & Dowell SF (1998) The common cold-principles of judicious use of antimicrobial agents. Pediatrics 101, 181–183. Snow V, Mottur-Pilson C & Gonzales R (2001) Principles of appropriate antibiotic use for treatment of nonspecific upper respiratory tract infections in adults. Annals of Internal Medicine 134, 487–489. Thamlikitkul V & Apisitwittaya W (2004) Implementation of clinical practice guidelines for upper respiratory infection in Thailand. International Journal of Infectious Diseases 8, 47–51. Tomaz A (1994) Multiple antibiotic-resistant pathogenic bacteria: a report on the Rockefeller University Workshop. New England Journal of Medicine 1994, 1247–1251. Van den Broek d’Obrenan J, Verheij TJM, Numans ME & vander Velden AW (2014) Antibiotic use in Dutch primary care: relation between diagnosis, consultation and treatment. Journal of Antimicrobial Chemotherapy doi: 10.1093/jac/dku005. Van Driel ML, de Sutter A, Deveugele M et al. (2006) At patients who hope for antibiotics actually asking for pain relief? The Annals of Family Medicine 4, 494–499. Van Gageldonk-Lafeber AB, Heijnen MLA & bartelds AIM, Peeters MF, van der Plas SM & Wilbrink B, (2005) A case-control study of acute respiratory tract infection in general practice patients in The Netherlands. Clinical Infectious Diseases 41, 490–497.
767
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Wattal C, Raveendran R, Kotwani A et al. (2009) Establishing a new methodology for monitoring of antimicrobial resistance and use in the community in a resource poor-setting. Journal of Applied Therapeutic Research 7, 37–45. Welschen I, Kuyvenhoven M, Hoes A & Verheij T (2004) Antibiotics for acute respiratory tract symptoms: patients’ expectations, GPs’ management and patient satisfaction. Family Practice 21, 234–237. WHO (2008) The Anatomical Therapeutic Chemical Classification System with Defined Daily Doses (ATC/DDD). WHO,
Norway, 2004. http://www.who.int/classifications/actddd/en. Accessed on October 22, 2010. WHO (2009a) Community-based surveillance of antimicrobial use and resistance in resource-constrained settings. Report on five pilot projects. http://www.who.int/medicines/publications/ who_emp_2009.2/en/index.html WHO (2009b) Medicines Use in Primary Care in Developing and Transitional Countries. Fact Book Summarizing Results from Studies Reported between 1990 and 2006. Available at: http://apps.who.int/medicinedocs/en/m/abstract/Js16073e/
Corresponding Author Anita Kotwani, Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi 110007, India. Tel.: + 91 11 27402404; Fax +91 11 27666549; E-mail: [email protected]
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Antibiotic prescribing practice for acute, uncomplicated respiratory tract infections in primary care settings in New Delhi, India Anita Kotwani1 and Kathleen Holloway2 1 Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi, India 2 Essential Drugs and Other Medicines, WHO, Regional Office for South East Asia, New Delhi, India
Abstract
objective To obtain information on prescribing rates and choice of antibiotics for acute, uncomplicated respiratory tract infections (RTIs) in the community. methods Antibiotic use in acute, uncomplicated RTIs consisting of common cold/sore throat/cough for not more than five days was surveyed in the community (December 2007–November 2008) using patient exit interviews at public and private facilities from four localities in New Delhi. Data were collected from 10 public sector facilities and 20 private clinics over one year. The percentage of acute, uncomplicated RTIs patients receiving antibiotics in general and using the Anatomical Therapeutic Chemical classification and the Defined Daily Dose (ATS/DDD) were analysed. results At public and private facilities, 45% (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed at least one antibiotic, respectively. The main antibiotic class calculated as percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI patients at private clinics was cephalosporins, J01DA (39%), followed by fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA (15%). Newer members from each class were prescribed; older antibiotics such as co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the main class of antibiotic prescribed was penicillins (31%), followed by macrolides (25%), fluoroquinolones (20%) and cephalosporins (10%). conclusions Study clearly shows overuse and inappropriate choice of antibiotics for the treatment of acute, uncomplicated RTIs which are mainly due to virus and do not require antibiotic treatment. Results of the study warrant interventional strategies to promote rational use of antibiotics to decrease the overgrowing threat of antibiotic resistance. keywords antibiotics prescribing, antibiotic resistance, community pharmacists, primary care, rational use of antibiotics, upper respiratory tract infections
Introduction Globally, antibiotic resistance is being recognised as a major healthcare issue; local, national and international efforts are needed to counteract its emergence. Antibiotic use is considered as a key contributor for the increase and spread of antibiotic resistance (Albrich et al. 2004). A major concern is the inappropriate use of antibiotics for non-bacterial infections and for self-limiting clinical conditions. Antibiotic usage in primary healthcare settings is high, and consumption of antibiotics for respiratory tract infections is the most common indication as documented for the developed world (Goossens et al. 2005). Upper respiratory tract infections (URTIs) are the most commonly treated acute problems in primary care
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(Thamlikitkul & Apisitwittaya 2004; Francis et al. 2009), with the majority of infections of viral origin (Mono 2002; Van Gageldonk-Lafeber et al. 2005). However, data from developing countries for antibiotic use for URTIs are scarce, and surveillance of antibiotic use in the community is not in place. Data and pattern on antibiotic use and resistance are prerequisite for development, implementation and assessment of antibiotic guidelines and for local and national prescribing policies (MalhotraKumar et al. 2004; Goossens et al. 2007). Upper respiratory tract infections or nasopharyngitis and colds are conditions that are most likely caused by viruses (Nyquist et al. 1998; Snow et al. 2001) and therefore do not require antibiotics (O’Brien et al. 1998; Rosentein et al. 1998; Avorn & Solomon 2000). 761
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Gadomski (1993) performed a meta-analysis addressing the treatment of non-specific URTIs and found that antibiotics neither shortened the length of upper respiratory illness nor prevented the development of pneumonia. The Centers for Disease Control (CDC) and the American Academy of Pediatrics (AAP) both advocate the same principle regarding the common cold that the use of antimicrobial agents should be avoided (Jacobs 2000). Children treated unnecessarily are at high risk for developing penicillin-resistant Streptococcus pneumonia (PRSP) (Tomaz 1994; Frick et al. 1998). Unfortunately, URTIs are common conditions for which the misuse of antibiotics is common and is reported from different parts of the world (Evans et al. 2005; Van den Broek d’Obrenan et al. 2014). Understanding the extent and pattern of antibiotics use for acute URTIs in the community is important for developing a regional intervention programme to promote the rational use of antibiotics and thus limits the spread of antimicrobial resistance for developing country where a surveillance system and antibiotic policy are generally not developed. Hence, this study was conducted in New Delhi, India. The primary aims of this study were (i) to find out the percentage of antibiotic prescriptions by primary healthcare providers in public and private sectors with acute, uncomplicated RTIs, the majority of which will be URTI, and (ii) to determine the pattern of antibiotic choice in public and private sectors for these conditions in New Delhi, India. As the diagnosis is generally not recorded on prescriptions, diagnosis had to be ascertained by asking patients about their symptoms. This made it difficult to separate URTI from LRTI. However, effort was made to focus on symptoms of acute, uncomplicated RTIs like common cold/sore throat and acute cough, the majority of which will be viral URTI and self-limiting. Findings about the use of antibiotics in such conditions will give some indication of inappropriate use of antibiotics and would be valuable in developing strategies to improve primary care doctors’ prescribing routine. This study was conducted from December 2007 to November 2008. Methods This study was part of a larger study on surveillance of antibiotic use and resistance in the community, and data were collected from four residential localities (municipal wards) of New Delhi, India. The four areas were as follows: Rajinder Nagar, Patel Nagar, Karol Bagh and Rajouri Garden. To get a complete picture of antibiotic use in the community for acute, uncomplicated RTIs, both public and 762
private sector facilities were surveyed. In the public sector, all eight dispensaries (primary healthcare facility) and two small hospitals (secondary care level) under Government of National Capital Territory of Delhi (GNCT, Delhi) in the study area were enrolled. At public facilities, prescribed medicines are provided free to the population if those medicines are available in the facility. Twenty private sector general practitioners and specialists willing to cooperate for the study, practising in the chosen areas, including four paediatricians, three physicians and 13 general practitioners (GPs) were included from the private sector. At private facilities, patients must pay for medicines. In the absence of community-based databases on antibiotic use, absence of disease-code classification, frequent absence of facility-based patient notes and doctors often not writing the diagnosis on the prescription, a method recently established for the surveillance of antibiotic use at New Delhi by conducting ‘exit interviews’ of the patients (Kotwani et al. 2009; WHO 2009a,b; Kotwani & Holloway 2011) was used. Patients were asked about symptoms which generally represent uncomplicated respiratory infections and are self-limiting. Data on antibiotic use were collected by trained data collectors (pharmacists) who conducted exit interviews of patients leaving the facility (Kotwani & Holloway 2011). Data collectors visited each public facility twice every month and private clinics thrice every month to collect the data. Data were collected from five private practitioners per month; the practitioners being randomly chosen every month were from a pool of 20 practitioners enrolled for the study. All the patients coming out from the prescriber’s office were asked whether they had common cold/sore throat/cough for the last 1–5 days and no persistent cough for more than five days. Data collectors also asked patients whether they had mentioned these same symptoms (common cold/sore throat/cough for the last 1–5 days) to the prescriber and whether the prescription they had received was for the same symptoms. Any patient with the above-mentioned symptoms was labelled as having acute, uncomplicated RTI and was enrolled for exit interview, and his/her prescription was monitored. Other patients who were classified as having severe diseases, for example cough for more than 5 days, a written diagnosis of pneumonia or otitis media in children, were excluded from the study. A pre-designed proforma was used to collect data regarding the name, dose and duration of antibiotic prescribed. Data collectors’ schedules were randomly prepared for the day and time (1 h) of visits every month for data collection.
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Antibiotic use was measured in terms of the percentage of acute, uncomplicated RTI patients receiving an antibiotic. To estimate this, the numerator was the number of acute, uncomplicated RTI patients receiving an antibiotic and the denominator was the total number of acute, uncomplicated RTI patients, whether or not they received antibiotics – both recorded during each facility visit for the time that the data collectors were in the facility. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were also assigned to the data (WHO 2008) to examine in detail the types of antibiotic prescribed. Prescribing patterns for various antibiotics in public and private clinics were analysed, and the consumption of each antibiotic was expressed as percentage of total number of DDDs/ 1000 acute, uncomplicated RTI patients attending all the public or private facilities. All data were entered into software developed in Visual Basic, SQL Server and Crystal Reports. The same software was used to analyse the data. Ethical approval for the study was obtained from Vallabhbhai Patel Chest Institute, University of Delhi, India, and also from WHO’s Ethics Review Committee.
Informed consent was obtained from all participants and facilities involved in the study. Results A total of 1646 acute, uncomplicated RTI patients from public facilities and a total of 457 acute, uncomplicated RTI patients from private clinics were studied. No clear seasonal variation in number of acute, uncomplicated RTI patients was observed at both public and private facilities. Percentage of prescriptions with antibiotics for acute, uncomplicated RTIs Table 1 shows the percentage of patients who were prescribed various antibiotics. At public facilities, 45% of acute URTI patients were prescribed at least one antibiotic. Subgroup analysis for two secondary care level study hospitals showed that 44% of acute, uncomplicated RTI patients were given antibiotics (Table 1). Doctors at both types of public facility, that is, dispensaries (primary healthcare facilities) and secondary level hospitals (30
Table 1 Percentage of prescriptions with various antibiotics in acute, uncomplicated respiratory tract infections in public sector and private clinics (December 2007–November 2008) Total no. of patients
Prescriptions with antibiotics
% Prescriptions with antibiotics
% Distribution of various antibiotics used
Public sector (hospitals + dispensaries)
1646
746
45.3
2
Public sector (hospitals)
294
131
44.5
3
Private clinics
457
259 * 4 patients received 2 antibiotics
56.7
4
Private clinics (paediatrics)
138
84* 3 patients received 2 antibiotics
60.9
Macrolides (29.3) Penicillins (26.3) Cephalosporins (16.2) Fluoroquinolones (13.1) Co-trimoxazole (9.4) Tetracycline (5.4) Nalidixic acid (0.13) Aminoglycosides (0.13) Penicillins (30.5) Macrolides (24.4) Cephalosporins (19.8) Fluoroquinolones (19.1) Co-trimoxazole (12.2) Tetracycline (3.1) Cephalosporins (40.0) Fluoroquinolones (21.7) Penicillins (19.7) Macrolides (16.3) Tetracycline (1.9) Co-trimoxazole (0.4) Cephalosporins (49.4) Penicillins (20.7) Fluoroquinolones (15) Macrolides (13.8) Co-trimoxazole (1.1)
No.
Sector
1
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and 50 bedded), prescribed antibiotics in a similar fashion. The highest consumption was for penicillins (J01C) and macrolides (J01FA), followed by cephalosporins (J01DA), fluoroquinolones (J01MA), co-trimoxazole (J01EF01) and tetracyclines (J01A). At private clinics, overall 57% of patients were prescribed any antibiotic for the treatment of acute, uncomplicated RTIs. On subgroup analysis for private clinics, the paediatricians prescribed antibiotics to 61% of children with acute, uncomplicated RTIs (Table 1). Both general physicians (GPs) and paediatricians mainly prescribed cephalosporins, followed by fluoroquinolones, penicillins and macrolides. The use of older antibiotics, such as co-trimoxazole or tetracyclines, was minimal (Table 1). Antibiotic prescription pattern in terms of DDDs for acute, uncomplicated RTIs Table 2 shows the number of DDDs for each class of antibiotics prescribed as a percentage of total DDDs for all antibiotics prescribed/1000 patients of acute, uncomplicated RTIs at public and private facilities surveyed. In the public sector, consumption in terms of DDDs shows that amoxicillin, ofloxacin and roxithromycin were the most commonly dispensed antibiotics for acute, uncomplicated RTIs. A few patients were also given older antibiotics such as erythromycin, doxycycline, ampicillin, cephalexin, cloxacillin, ciprofloxacin and tetracycline and relatively newer antibiotics such as amoxicillin+clavulanic acid and cefuroxime. In the private sector, consumption in terms of DDDs shows that newer antibiotics such as cefuroxime, cefpodoxime, cefixime and cefixime+clavulanic acid, levofloxacin, ofloxacin and roxithromycin were the most commonly prescribed antibiotics for acute, uncomplicated RTIs (Table 2). Older antibiotics were not generally used. Discussion Our study revealed that antibiotic prescriptions for acute, uncomplicated RTIs were common in primary care settings, more so in the private sector (57%) than in the public sector (45%). We focused on acute, uncomplicated RTI, most of which will have been viral URTI. It is unlikely that 40% or more of such patients would have had lower RTI requiring antibiotics, so the proportion of patients prescribed antibiotics would appear to be high. Other studies have also described antibiotic prescribing for non-specific RTI diagnosis. In primary care settings in the Netherlands (Van den Broek d’Obrenan et al. 2014), 764
Table 2 Pattern of antibiotic use for acute, uncomplicated respiratory tract infections in private and public facilities surveyed in Delhi, India (December 2007–November 2008)
Antibiotic name Cephalosporins J01DA Cefuroxime Cefpodoxime proxetil Cephalexin Cefixime Cefixime + clavulanic acid Cefaclor Others Fluoroquinolones J01MA Levofloxacin Ofloxacin Ciprofloxacin Norfloxacin Penicillins J01C Amoxicillin+clavulanic acid Amoxicillin Amoxicillin+cloxacillin Ampicillin Cloxacillin Macrolides J01FA Roxithromycin Azithromycin Erythromycin Tetracycline J01A Doxycycline Tetracycline Demeclocycline Combinations of sulphonamide with Trimethoprim (J01EE) Co-trimoxazole Total
Private clinics% of total DDDs of antibiotic prescribed to RTI patients 39.1 11.9 8.6 0.6 8.5 8.2 0.4 0.9 23.6 12.7 8.7 2.2 – 19.1 14.0 3.0 2.1 – 15.5 11.4 4.0 0.1 2.7 2.7
0.03
0.03 100
Public sector% of total DDDs for antibiotic prescribed to RTI prescribed 10.4 6.7 – 3.7 – – – 19.7 – 15.6 3.7 0.4 31.0 7.5 15.9 0.2 4.4 3.0 24.6 14.7 – 9.9 9.5 7.1 2.3 0.05 4.8
4.8 100
overall antibiotics were prescribed in approximately 25% of infectious disease episodes – amongst respiratory infections, for acute upper RTI approximately 20% and for cough approximately 16% of episodes. In primary care settings in Ireland (Murphy et al. 2012), there was considerable antibiotic prescribing for conditions not included in the guidelines such as URTI (33.1%), cough (35.8%) and sore throat (53.1%). In Poland, more than half of patients (54.2%) with a common cold were treated with an antibiotic (Panasiuk et al. 2010). Comparison with these data clearly shows that the percentage of patients who receive antibiotics for acute, uncomplicated RTIs in the present study at primary care was high. A
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WHO review of studies showed high antibiotic use for URTIs globally and in the Asia (WHO 2009a,b). The other important finding was the choice of antibiotic prescribed for these acute and uncomplicated symptoms such as common cold or sore throat or cough. In India, we do not have national or regional well-recognised official guidelines for the treatment of common diseases and infections for primary care settings. Moreover, the prescriptions in the private sector are not officially regulated. However, the Government of National Capital Territory of Delhi (GNCT) has an essential medicine list (EML), and this EML is separate for primary care and tertiary care hospitals. Procurement is supposed to be based on EML, and doctors are supposed to prescribe from it. The EML 2007 applicable at the time of the study for primary care comprised the following antibiotics: benzathine penicillin and procaine penicillin (powder for injection), amoxicillin, ampicillin, cloxacillin, ciprofloxacin, norfloxacin, nalidixic acid, erythromycin, roxithromycin, sulphamethoxazole + trimethoprim and doxycycline. Cephalexin was mentioned for restricted use only. These antibiotics are usually first-line or second-line choice for common infections and should be prescribed at primary care. The survey revealed that all antibiotics on the list of Delhi state EML, even those which were supposed to be reserve antibiotics for hospitals, such as third-generation cephalosporins (e.g. cefuroxime) and fluoroquinolones (e.g. levofloxacin) and amoxicillin+clavulanic acid, were available and used in dispensaries (primary healthcare facilities) as found in earlier surveys conducted in Delhi State (Kotwani & Holloway 2011, 2013; Kotwani et al. 2012). Thus, public procurement and distribution did not appear to be following the EML. At private clinics, where no official guidelines or EML is implemented, the pattern of antibiotic use was different. In India, around 80% of the population rely on private health care (Creese et al. 2004). The present survey revealed that second- and third-generation cephalosporins and other antibiotics such as levofloxacin, ofloxacin, amoxicillin+clavulanic acid and roxithromycin were prescribed for acute, uncomplicated RTIs. First-generation or first-line antibiotics such as co-trimoxazole, ampicillin, amoxicillin and erythromycin were rarely prescribed in private clinics. The above-mentioned three studies from the Netherlands, Ireland and Poland have shown a different pattern of antibiotic use in primary care for RTIs. In the Netherlands (Van den Broek d’Obrenan et al. 2014) for all respiratory infections, tetracyclines and amoxicillin accounted for about 65% of prescriptions and the prescription of macrolides and amoxicillin/clavulanate was about 14% and 10%, respectively. In Ireland (Murphy
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et al. 2012) for tonsillitis, 43% patients were prescribed phenoxypenicillin, which is the first-line antibiotic, and 20% amoxicillin and 25% co-amoxiclav, which are second-line antibiotics according to Irish national guidelines for the treatment of tonsillitis. In Poland (Panasiuk et al. 2010), high percentage of amoxicillin use for common cold, pharyngitis, tonsillitis and URTI of multiple or unspecified sites was reported. All these studies reported either minimal or no use of second- and third-generation cephalosporins or fluoroquinolone for common cold, pharyngitis, sinusitis and cough. In comparison with these studies, our survey showed that not only high antibiotic was high but also the choice of antibiotic for the treatment of acute, uncomplicated RTIs was also inappropriate. A qualitative study conducted with prescribers of both public and private sector facilities of the same municipal wards of Delhi where this study was conducted (Kotwani et al. 2010) revealed that private practitioners’ first important reason for prescribing antibiotic is financial consideration to not lose the patient to another doctor who will prescribe an antibiotic. The various other reasons doctors put forth for prescribing antibiotics were: diagnostic uncertainty whether infection is bacterial or viral; they perceive expectation for antibiotic prescription from patients; and to satisfy the patient by giving something more than just paracetamol. Doctors from public sector facilities mentioned that because of patient overcrowding, they do not have enough time to explain to the patients that antibiotics are not needed. These findings indicate that antibiotics are misused by many doctors for the treatment of acute, uncomplicated RTIs either due to financial gain and ignorance or due to various other perceived pressures. Similar behaviour and findings for doctors have been observed by other researchers (Van Driel et al. 2006). Other studies report that only a small proportion of patients explicitly expect a prescription, and even if they do, their primary concern is to find symptomatic relief (Altiner et al. 2004; Van Driel et al. 2006); patients were satisfied with careful examination and reassurance, irrespective of whether they received an antibiotic or not (Welschen et al. 2004; van Duijn et al. 2007; Fischer et al. 2008). Similar studies with respect to patients’ concerns, beliefs and satisfaction are urgently needed in developing countries. A qualitative study conducted by Kotwani et al. (2012) for retail pharmacists in these same residential areas of Delhi revealed that pharmacists mimic the prescription of neighbourhood general practitioners and they themselves prescribe and dispense antibiotics for one or two days for acute, uncomplicated RTIs. Therefore, it is very important that doctors prescribe antibiotics rationally, as their prescription is copied 765
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by others who are actually not legally entitled to prescribe antibiotics. Surveillance of antibiotic use in these same localities in New Delhi has shown a high use of fluoroquinolones and markedly increasing use of cephalosporins from 2004 to 2008 (Kotwani & Holloway 2011). The sales data indicate that overall units of antibiotic sold in India between 2005 and 2009 increased by about 40%. Increased sales of cephalosporins were particularly striking, increasing by 60% over that five-year period (Ganguly et al. 2011). This increase in use of cephalosporins is worrying from the prospective of increasing resistance to them. Our study also indicates the increasing use of cephalosporins in acute, uncomplicated RTIs in the private sector. Irrational use of cephalosporins in these communities is resulting in resistance observed in E. coli (Wattal et al. 2009), and the continuous overuse will increase the antimicrobial resistance. Growing antimicrobial resistance has become a worldwide health threat, and it is worrisome because of the dearth of new antibiotics being developed. The need for prompt action by all countries is urgently required to avert this developing global crisis. Surveillance of antibiotic use is one of the strategies to guide control of antibiotic overuse or misuse. Based on the country- or regionspecific data on pattern of antibiotic use, policy and guidelines for rational use of antibiotics should be prepared and implemented strictly. Quality assurance programmes and public campaigns have been developed and launched in Europe to improve the use of antibiotics in primary care (Welschen et al. 2004; Goossens et al., 2006; MacReady 2009). The positive effects reported with these projects suggest that their implementation in other countries with high antibiotic prescribing may be effective. In India, there is an urgent need to develop and implement treatment guidelines at primary care settings for rational use of antibiotics. The strength of this study is that it clearly shows that it is possible to collect useful data for antibiotic use in both public and private sector facilities, at the individual patient level in resource-constrained settings where a database is not available. This is one of the few studies conducted in India that have shown prescribing pattern of antibiotics for the treatment of acute, uncomplicated respiratory tract infections in both public and private sectors. Findings of this study can be useful for conducting intervention studies to improve rational use of antibiotics in acute RTIs. The study has some inherent weaknesses. Firstly, it was conducted in four residential localities of one urban area, so generalisation should be done with caution for the rest of Delhi and cannot be done for other areas of India. Secondly, the presence of data 766
collectors may have changed the prescribing habits of doctors at private clinics. Doctors may have prescribed fewer antibiotics than normally. In public facilities, the bias introduced into doctors’ prescribing may have been less as the data collectors were in the pharmacy area and doctors were not always aware which day and time data collectors were visiting. Misclassification as to whether patients were suffering from lower or upper respiratory tract infection may have occurred, but lack of recorded information on diagnosis meant that a patient interview was the only way to identify cases of acute, uncomplicated RTI. Nevertheless, care was taken to exclude as far as possible cases of RTI that may have needed antibiotics, and it is likely that there were only a small proportion of such cases. Conclusions and recommendations This study shows a high use of antibiotics by primary care doctors for the treatment of acute, uncomplicated respiratory tract infections, most of which will be self-limiting viral URTI. Choice of antibiotic was more inappropriate in private clinics, where cefuroxime, cefpodoxime proxetil, cefixime+clavulanic acid and amoxicillin+clavulanic acid were the main antibiotics prescribed. Standard treatment guidelines for the treatment of respiratory tract infections need to be urgently developed and strictly implemented in both public and private sectors in India. Acknowledgements We thank all the participating doctors, hospital in charge, Directorate Medical Services, Government of NCT, Delhi, and patients for their cooperation and support during the study. The project was funded by WHO.
References Albrich WC, Monnet DL & Harbarth S (2004) Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes. Emerging Infectious Disease 10, 514– 517. Altiner A, Knauf A, Moebes J, Sielk M & Wilm S (2004) Acute cough: a qualitative analysis of how GPs manage the consultation when patients explicitly or implicitly expect antibiotic prescriptions. Family Practice 21, 500–506. Avorn J & Solomon D (2000) Cultural and economic factors that (mis)shape antibiotic use: the nonpharmacologic basis of therapeutics. Annals of Internal Medicine 133, 128–135. Creese A, Kotwani A, Kutzin J. & Pillay A (2004) Evaluating pharmaceuticals for health policy in low and middle income country settings. In: Evaluating pharmaceuticals for health
© 2014 John Wiley & Sons Ltd
Tropical Medicine and International Health
volume 19 no 7 pp 761–768 july 2014
A. Kotwani & K. Holloway Antibiotic prescription practices in New Delhi
policy and reimbursement (eds N Freemantle & S Hill) Blackwell Publishing, BMJ Books and WHO, Massachusetts, pp. 227–243. van Duijn HJ, Kuyvenhoven MM, Schellevis FG & Verheij TJM (2007) Illness behaviour and antibiotic prescription in patients with respiratory tract symptoms. British Journal of General Practice 57, 561–568. Essential Medicine List (2007) Government of NCT Delhi. http://www.scribd.com/doc/12401543/Drug-list Evans CT, Smith B, Parada JP, Kurich JE & Weaver FM (2005) Trends in antibiotic prescribing for acute respiratory infections in veterans with spinal cord injury and disorder. Journal of Antimicrobial Chemotherapy 55, 1045–1049. Fischer T, Fischer S, Himmel W, Kochen MM & Hummers PE (2008) Family practitioners’ diagnostic decision-making processes regarding patients with respiratory tract infections: an observational study. Medical Decision Making 28, 810–818. Francis NA, Butler CC, Hood K, Simpson S, Wood F & Nuttal J (2009) Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster-randomised controlled trial. British Medical Journal 339b, 2885. Frick PA, Black DJ, Duchin JS, Deliganis S, McKee WM & Fritsche TR (1998) Prevalence of antimicrobial drug-resistant Streptococcus pneumoniae in Washington State. Western Journal of Medicine 169, 364–369. Gadomski AM (1993) Potential interventions for preventing pneumonia among young children:lack of effect of antibiotic treatment for respiratory infections. The Pediatric Infectious Disease Journal 12, 115–120. Ganguly NK, Arora NK, Chandy SJ et al. (2011) Rationalizing antibiotic use to limit antibiotic resistance in India. Indian Journal of Medical Research 134, 281–294. Goossens H, Guillemot D, Ferech M et al. (2006) National campaigns to improve antibiotic use. European Journal of Clinical Pharmacology 62, 373–379. Goossens H, Ferech R, Stichele RV & Elseviers M (2005) Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365, 579–587. Goossens H, Ferech M, Coenen S & Stephens P (2007) European surveillance of antimicrobial consumption project group. Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries. Clinical Infectious Disease 44, 1091–1095. Jacobs RF (2000) Judicious use of antibiotics for common pediatric respiratory infections. Pediatric Infectious Diseases 19, 938–940. Kotwani A & Holloway K (2011) Trends in antibiotic use among outpatients in New Delhi, India. BMC Infectious Diseases 11, 99. Kotwani A & Holloway K (2013) Access to antibiotics in New Delhi, India: implications for antibiotic policy. Journal of Pharmaceutical Policy and Practice 6, 6. Kotwani A, Holloway K & Chaudhury RR (2009) Methodology for surveillance of antimicrobials use among out-patient in Delhi. Indian Journal of Medical Research 129, 555–560.
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Kotwani A, Wattal C, Katewa S, Joshi PC & Holloway K (2010) Antibiotic use in the community: what factors influence primary care physicians to prescribe antibiotics in Delhi, India? Family Practice 27, 684–690. Kotwani A, Wattal C, Katewa S, Joshi PC & Holloway K (2012) Irrational use of antibiotics and role of pharmacists: an insight from a qualitative study in New Delhi, India. Journal of Clinical Pharmacy and Therapeutics 37, 308–312. MacReady N (2009) French campaign reduces antibiotic prescriptions. The Lancet Infectious Diseases 9, 469. Malhotra-Kumar S, lammens C, Piessens J & Goossens H (2004) Oropharyngeal carriage of macrolide-resistant viridans group streptococci : a prevalence study among healthy adults in Belgium. Journal of Antimicrobial Chemotherapy 53, 271–276. Mono AS (2002) Epidemiology of viral respiratory infections. American Journal of Medicine 112(suppl 6A), 4S–12S. Murphy M, Bradley CP & Byone S (2012) Antibiotic prescribing in primary care, adherence to guidelines and unnecessary prescribing – an Irish perspective. BMC Family Practice 13, 43. Nyquist AC, Gonzales R & Steiner Sande MA (1998) Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. Journal of the American Medical Association 279, 855–877. O’Brien KL, Dowell SF & Schwartz B (1998) Acute sinusitisprinciples of judicious use of antimicrobial agents. Pediatrics 101, 174–176. Panasiuk L, Lukas W, Paprzycki P, Verheij T, Godycki-Cwirko M & Chlabicz S (2010) Antibiotics in the treatment of upper respiratory tract infections in Poland. Is there any improvement? Journal of Clinical Pharmacy & Therapeutics 35, 665– 669. Rosentein N, Philips WR, Gerber MA, Marcy SM, Schwartz B & Dowell SF (1998) The common cold-principles of judicious use of antimicrobial agents. Pediatrics 101, 181–183. Snow V, Mottur-Pilson C & Gonzales R (2001) Principles of appropriate antibiotic use for treatment of nonspecific upper respiratory tract infections in adults. Annals of Internal Medicine 134, 487–489. Thamlikitkul V & Apisitwittaya W (2004) Implementation of clinical practice guidelines for upper respiratory infection in Thailand. International Journal of Infectious Diseases 8, 47–51. Tomaz A (1994) Multiple antibiotic-resistant pathogenic bacteria: a report on the Rockefeller University Workshop. New England Journal of Medicine 1994, 1247–1251. Van den Broek d’Obrenan J, Verheij TJM, Numans ME & vander Velden AW (2014) Antibiotic use in Dutch primary care: relation between diagnosis, consultation and treatment. Journal of Antimicrobial Chemotherapy doi: 10.1093/jac/dku005. Van Driel ML, de Sutter A, Deveugele M et al. (2006) At patients who hope for antibiotics actually asking for pain relief? The Annals of Family Medicine 4, 494–499. Van Gageldonk-Lafeber AB, Heijnen MLA & bartelds AIM, Peeters MF, van der Plas SM & Wilbrink B, (2005) A case-control study of acute respiratory tract infection in general practice patients in The Netherlands. Clinical Infectious Diseases 41, 490–497.
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A. Kotwani & K. Holloway Antibiotic prescription practices in New Delhi
Wattal C, Raveendran R, Kotwani A et al. (2009) Establishing a new methodology for monitoring of antimicrobial resistance and use in the community in a resource poor-setting. Journal of Applied Therapeutic Research 7, 37–45. Welschen I, Kuyvenhoven M, Hoes A & Verheij T (2004) Antibiotics for acute respiratory tract symptoms: patients’ expectations, GPs’ management and patient satisfaction. Family Practice 21, 234–237. WHO (2008) The Anatomical Therapeutic Chemical Classification System with Defined Daily Doses (ATC/DDD). WHO,
Norway, 2004. http://www.who.int/classifications/actddd/en. Accessed on October 22, 2010. WHO (2009a) Community-based surveillance of antimicrobial use and resistance in resource-constrained settings. Report on five pilot projects. http://www.who.int/medicines/publications/ who_emp_2009.2/en/index.html WHO (2009b) Medicines Use in Primary Care in Developing and Transitional Countries. Fact Book Summarizing Results from Studies Reported between 1990 and 2006. Available at: http://apps.who.int/medicinedocs/en/m/abstract/Js16073e/
Corresponding Author Anita Kotwani, Department of Pharmacology, V. P. Chest Institute, University of Delhi, Delhi 110007, India. Tel.: + 91 11 27402404; Fax +91 11 27666549; E-mail: [email protected]
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