Antimicrobial Original Research Paper
Prescription of antibiotics and awareness of antibiotic costs by paediatricians in two hospitals in Greece Helena C. Maltezou1, Katerina Mougkou2, Elias Iosifidis3, Panos Katerelos1, Emmanuel Roilides3, Maria Theodoridou2 1
Department for Interventions in Health-Care Facilities, Hellenic Center for Diseases Control and Prevention, Athens, 21st Department of Pediatrics, University of Athens, ‘Aghia Sophia’ Children’s Hospital, Athens, 33rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration Hospital, Thessaloniki, Greece Our aim was to study the antibiotic prescription practices and the knowledge about antibiotic costs, brand and generic drugs of paediatricians working in two hospitals in Greece. The 2007 national guidelines were used as the gold standard for antibiotic prescription. A total of 126 paediatricians participated in the study (50.4% response rate). The mean compliance rate with the guidelines was 50.1% (range per infection: 10.6–84.7%). The mean scores of knowledge about antibiotic costs and about brand name and generic drugs were 35.6 and 60.3%, respectively. Linear regression analysis found a significant association between the mean compliance rate with the national guidelines and the paediatricians’ age (mean compliance rates were 49.1, 53.0, and 43.0% in the # 30, 31–40, and . 40 years age-groups, respectively; P 5 0.003). In conclusion, five years after the first national guidelines were issued in Greece only half of the paediatricians working in hospitals comply fully with them. Keywords: Antibiotics, Paediatrician, Hospital, Prescription, Cost
Introduction The use of antimicrobial agents in clinical practice in the second half of the twentieth century constituted a major achievement in medical history, leading to the prevention, treatment and control of several fearful infectious diseases of the past. However, the emergence and spread of antibiotic resistant or multiresistant pathogens globally in association with the unavailability of novel antibiotics is a public health threat.1,2 Unnecessary or inappropriate antibiotic use in the hospital setting and the community strongly contributes to the emergence of resistant pathogens. Thus, the limitation of unnecessary antibiotic use or misuse has become a public health priority globally.3,4 Greece is amongst the European countries with the highest rates of consumption of antibiotics and antibiotic resistance.5,6 Given this situation, the Hellenic Center for Diseases Control and Prevention (HCDCP) issued guidelines in 2007 in order to promote the rational use of antibiotics by physicians in hospitals and community settings. These guidelines were printed in pocket books and subsequently Correspondence to: Dr Helena C. Maltezou, Department for Interventions in Health-Care Facilities, Hellenic Center for Diseases Control and Prevention, 3-5 Agrafon Street, Athens, Greece. Email: helen-maltezou@ ath.forthnet.gr
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distributed to all hospital-based physicians. These guidelines are also available at the HCDCP website.7 Furthermore, the use of generic over brand name drugs is being promoted by the Ministry of Health the past two years, in order to reduce the health-associated expenditures within the current economic crisis. The aim of this study was to evaluate the antibiotic prescription practices for common infections among hospital-based paediatricians in Greece, using the HCDCP guidelines as the gold standard. The paediatricians’ knowledge about antibiotic costs, brand name and generic drugs was also studied.
Methods Primary objectives of the study were: (1) the estimation of the compliance of the paediatricians with the first recommended antibiotic; (2) the estimation of the compliance of the paediatricians with the first and the alternative recommended antibiotics; (3) the estimation of the knowledge of the paediatricians about antibiotic costs; and (4) the estimation of the knowledge of the paediatricians about brand and generic drugs. Secondary objectives were the investigation of any possible association of the abovementioned with the characteristics of the paediatricians.
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Figure 1 Antibiotic prescription practices and knowledge about antibiotics, brand name and generic drugs of hospital-based paediatricians
Two major hospitals were selected, Aghia Sophia Children’s Hospital in Athens (central/south Greece) and Hippokrateion General Hospital in Thessaloniki (north Greece), where a total of 292 paediatricians
are employed. During March 2012 a standardized questionnaire was distributed to 250 paediatricians (42 paediatricians were not available), irrespective of personal or professional characteristics (Fig. 1).
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Figure 1 Continued
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Paediatricians were asked to complete the questionnaire anonymously and return it within the next day. The completed questionnaires were sent to HCDCP for data entry and analysis. The following data were collected using one form per paediatrician: age, gender, hospital of practice, qualification(s) and year(s) of acquisition of qualification(s). In order to evaluate the paediatricians’ first-line empiric treatment choices, six scenarios for common infections in children were provided. In addition, there were six questions about the costs of common antibiotic regimens and five questions about brand name and generic drugs. The costs of common antibiotic regimens were estimated for a 20-kg child. A 95% confidence interval (CI) was computed for each of the four scores (finite population correction was applied since the total number of hospital paediatricians in Greece is approximately 1500) (Hellenic Statistical Authority; personal communication). Multiple linear regression (forward selection) was applied in order to identify which paediatricians characteristics (age and/or gender) are significantly associated with their compliance rates with the 2007 national guidelines. The following univariate tests were also used: t-test for gender and Pearson correlation coefficient for age. An association was regarded as reliable if it was traced by both the regression technique and the respective univariate test. The time (years) since the acquisition of the medical diploma and the time (years) since the acquisition of the paediatric specialty diploma were not included in the regression model due to missing values. Pearson correlation coefficient was applied to investigate the possible association between the rates of compliance with the national guidelines and the two knowledge scores. P values of 0.05 or less were considered statistically significant. The STATA 8.0 software was used for the statistical analysis software (StataCorp LP, College Station, TX, USA).
Results A total of 126 paediatricians participated in the study (50.4% response rate). Participants were mainly female (74.1%), had a mean age of 37.6 years (range: 27–66 years), had graduated from a medical school a mean of 15.7 years (range: 1–32 years) ago, and had completed their paediatric residency program a mean of 8.9 years (range: 1–41 years) ago. The paediatricians’ first choice for common infections and the antibiotics recommended for the respective infections in accordance with the 2007 national guidelines are depicted in Table 1. Compliance rates with the guidelines in terms of the first recommended antibiotic were 84.7% for bacterial skin infection, 71.4% for streptococcal pharyngitis, 65.9% for acute otitis media, 41.4% for bacterial
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pneumonia requiring admission in the hospital, 27.8% for bacterial community-acquired pneumonia, and 10.6% for urinary tract infection. Compliance rates with the guidelines using the first and the alternative recommended antibiotics as the gold standard was 100% for acute otitis media and bacterial pneumonia requiring hospitalization, 95.2% for bacterial skin infection, 84.1% for streptococcal pharyngitis, 53.2% for bacterial communityacquired pneumonia, and 58.5% for urinary tract infection. The highest variation in antibiotic prescription was noted in the scenario about a 9-year-old child with community-acquired pneumonia (nine antibiotics of whom six beyond the national guidelines). In terms of specific antibiotics, amoxicillin/ clavulanate (alone or in combination) was the most frequent antibiotic prescribed beyond the guidelines, accounting for 41.5, 36.5, and 14.3% of prescriptions for urinary tract infection, bacterial communityacquired pneumonia, and streptococcal pharyngitis, respectively. The overall mean compliance rate of paediatricians with the guidelines was 50.1% (standard deviation: 617.7; 47.2–53.1% 95% CIs) for the first recommended antibiotic and reached 82.0% (standard deviation: 613.5; 79.7–84.2% 95% CIs) when the first and the alterative recommended antibiotics were considered. In terms of the paediatricians’ knowledge about the cost of common antibiotic regimens in paediatrics, correct answers ranged from 27.9% for a 10-day regimen of clarithromycin to 79.4% for a 10-day regimen of penicillin V (Table 2). The overall mean score of knowledge about antibiotic costs was 35.6% (standard deviation: 617.9; 32.3–38.8% 95% CIs) Regarding the paediatricians’ knowledge about brand-name and generic drugs, correct answers ranged from 11.7 to 80%; the overall mean score of knowledge about brand name and generic drugs was 60.3% (standard deviation: 625.2; 56.1–64.6% 95% CIs). Linear regression analysis found a significant association between the mean compliance rate with the national guidelines in terms of the first antibiotic choice and the paediatricians’ age. In particular, the mean compliance rates with the first recommended antibiotic were 49.1, 53.0, and 43.0% in the # 30, 31–40, and . 40 years age-groups, respectively (linear regression P value 5 0.003/Pearson Correlation Coefficient 5 20.256, P value 5 0.007). No significant association between the paediatricians’ characteristics and their compliance rates with the first and the alternative recommended antibiotics was found, as well as between their characteristics and their knowledge scores about antibiotic costs, brand name drugs and generic drugs (data not shown). Lastly, a statistically significant association was found between the paediatricians’ compliance rate with the first recommended antibiotic
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Table 1 Antibiotic prescription by hospital-based paediatricians for common community-acquired infections n (%) Recommended antibiotic1
Infection/antibiotic a. Streptococcal pharyngitis Penicillin V Amoxicillin/clavulanate Amoxicillin Clarithromycin Other b. Bacterial CAP in a 9-year-old outpatient child Amoxicillin/clavulanate Clarithromycin Amoxicillin Amoxicillin/clavulanate & clarithromycin Amoxicillin & clarithromycin Penicillin V Cefuroxime Amoxicillin & cefuroxime Cefuroxime & clarithromycin Other c. Febrile UTI in a 2-year-old child Amoxicillin/clavulanate Cefuroxime Cefaclor Trimethoprim/sulphamethoxazole Amoxicillin Cefixime d. Bacterial skin infection Amoxicillin/clavulanate Clindamycin Penicillin V Macrolide Trimethoprim/sulphamethoxazole Other e. AOM in a 2-year-old child Amoxicillin Amoxicillin/clavulanate 2nd or 3rd generation cephalosporin Clarithromycin Other f. Bacterial pneumonia in a 3-year-old outpatient child Amoxicillin/clavulanate Ampicillin Cefuroxime Penicillin V Clarithromycin
1st choice
N 5 126
90 18 12 4 2
(71.4) (14.3) (9.5) (3.2) (1.6)
34 30 28 12 8 6 3 2 1 2
(27.0) (23.8) (22.2) (9.5) (6.3) (4.8) (2.4) (1.6) (0.8) (1.6)
51 27 18 13 10 4
(41.5) (22.0) (14.6) (10.6) (8.1) (3.3)
1st choice 1st choice Alternative choice Alternative choice
74 31 9 4 3 3
(59.7) (25.0) (7.3) (3.2) (2.4) (2.4)
1st choice Alternative choice Alternative choice
83 27 6 6 4
(65.9) (21.4) (4.8) (4.8) (3.2)
1st choice
52 43 19 10 2
(41.3) (34.1) (15.1) (7.9) (1.6)
Alternative choice Alternative choice
1st choice Alternative choice
1st choice Alternative choice alternative choice
Alternative Alternative 1st choice Alternative Alternative
choice choice choice choice
Alternative choice
Note: 1In accordance with the Hellenic Center for Disease Control and Prevention 2007 guidelines. CAP: community-acquired pneumonia; UTI: urinary tract infection; AOM: acute otitis media.
and the alternative recommended antibiotics (Pearson Correlation Coefficient 5 0.330, P value , 0.001). No association was found between the compliance rates with the guidelines and the two knowledge scores (about antibiotic costs and brand name and generic drugs), as well as between the two knowledge scores (data not shown).
Discussion The current study was conducted in order to record the antibiotic prescription practices by hospital-based paediatricians in Greece five years after the first national guidelines about the use of antibiotics were issued. To the best of our knowledge, only few similar studies have been published so far.8–10 Our study revealed gaps in antibiotic prescription, with only one every two hospital-based paediatricians complying
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fully with the guidelines in terms of first antibiotic choice. We found even lower compliance rates (37.4%) among private paediatricians in the same country (unpublished data). In the current study, compliance rates ranged widely depending on infectious indication, from as low as 10.6% for urinary tract infection to 84.7% for bacterial skin infection. Overall, amoxicillin/clavulanate, a broad-spectrum antibiotic, was the first choice for a wide range of indications. The low compliance with the national guidelines may be attributed to gaps in knowledge about the rational use of antibiotics, the paediatricians’ unfamiliarity with the guidelines, but also to difficulties to modify their perceptions and attitudes towards antibiotic use. In this study paediatricians older than 40 years of age were less likely to comply with the national
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Table 2 Knowledge of costs regimens by paediatricians Antibiotic/cost (Euros)*
for
common
antibiotic
Number of paediatricians (%)
Amoxicillin/clavulanate (50 mg/kg/d, tid for 10 days) (n 5 111) 5–10 24 (21.6) 11–20 59 (53.2) (correct) 21–30 28 (25.2) Clarithromycin (20 mg/kg/d, bid for 10 days) (n 5 111) 10–20 31 (27.9) (correct) 21–40 66 (59.5) 41–60 14 (12.6) Penicillin V (50 000 IU/kg/d, x4 for 10 days) (n 5 107) 5–15 85 (79.4) (correct) 16–25 20 (18.7) 26–35 2 (1.9) Trimethoprim/sulphamethoxazole (10 mg/kg/d, bid for 10 days) (n 5 110) 1–10 49 (44.5) (correct) 11–20 50 (45.5) 21–30 11 (10.0) Cefaclor (40 mg/kg/d, tid for 10 days) (n 5 109) 5–15 25 (22.9) 16–25 67 (61.5) (correct) 26–35 17 (15.6) Cefotaxime (150 mg/kg/d, tid for 10 days) (n 5 109) 50–100 36 (33.0) 101–200 37 (34.0) (correct) 201–300 36 (33.0) Note: *Estimated for a 20-kg child.
guidelines. This finding is in accordance with other studies showing that physicians in longer practice are more likely to prescribe antibiotics inappropriately.11,12 Courses about the rational antibiotic use and prescription behaviour have been incorporated in modern medical and residency curricula the past two decades, which may explain the abovementioned differences. In addition, in contrast to older physicians, younger physicians may use more frequently electronic sources, which may also contribute to the higher compliance rates with the national guidelines among the latter. The overall awareness of the costs of commonly prescribed antibiotic regimens was generally inadequate. It has been shown that information about costs may be an important factor in decision making and thus reduce health-care expenditures.13 We also found gaps in the paediatricians’ knowledge about brand name and generic drugs. Gaps in knowledge about brand name and generic drugs may limit the adoption of the latter by the medical community in this country. Our study had three potential limitations. Firstly, the participating paediatricians may not reflect precisely all hospital-based paediatricians in Greece. However, the precision of the mean values and the CIs of all our primary objectives studied were very high, indicating that the primary objectives were approached with a very high accuracy. Secondly, there are no prior data to compare the paediatricians’ prescription practices before and after the issuance of the 2007 guidelines. Thirdly, there is a possibility of
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differentiation between the stated practices and realtime practice.14 However, our study provides information about the paediatricians’ antibiotic prescription practices and their knowledge about antibiotic costs. In conclusion, our study indicates that five years after the HCDCP issued the first national guidelines for antibiotic use in Greece, only half of the paediatricians working in two hospitals complied fully with them. Educational campaigns to promote the rational use of antibiotics by paediatricians and improve their prescription behaviour are warranted.
Acknowledgements We would like to thank the paediatricians for completing the questionnaires. We also thank Vasia Tsoutsa for technical assistance.
References 1 Maltezou HC. Metallo-b-lactamases in Gram-negative bacteria: introducing the era of pan-resistance? Int J Antimicrob Agent. 2009;33:405.e1–7. 2 French GL. The continuing crisis in antibiotic resistance. Int J Antimicrob Agent. 2010;3653:53–7. 3 World Health Organization. The evolving threat of antimicrobial resistance. Options for action. Geneva: WHO Press; 2012. 4 Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health. A public health action plan to combat antimicrobial resistance [document on the Internet]. [cited 2012 December 20]. Available from: http:// www.cdc.gov/drugresistance/pdf/public-health-action-plan-com bat-antimicrobial-resistance.pdf 5 European Surveillance of Antimicrobial Consumption. Consumption in Greece. [document on the Internet]. [cited 2012 December 20]. Available from: http://app.esac.ua.ac.be/ public/index.php/el_gr/antibiotic/in-your-country 6 European Centre for Disease Prevention and Control. European Antimicrobial Resistance Surveillance System Annual Reports. [document on the Internet]. [cited 2012 December 20]. Available from: http://ecdc.europa.eu/en/activities/ surveillance/EARS-Net/publications/Pages/documents.aspx 7 Hellenic Center for Disease Control and Prevention. Guidelines for the diagnosis and empiric treatment of infections, Athens 2007. [document on the Internet]. [cited 2012 December 20]. Available from: http://www.keelpno.gr/el-gr/diahe´simouliko´/ e´ntupouliko´.aspx [in Greek]. 8 Mckay RM, Vrbova L, Fuertes E, Chong M, David S, Dreher K, et al. Evaluation of the Do Bugs Need Drugs? Program in British Columbia: Can we curb antibiotic prescribing? Can J Infect Dis Med Microbiol. 2011;22:19–24. 9 Smith MJ, Kong M, Cambon A, Woods CR. Effectiveness of antimicrobial guidelines for community-acquired pneumonia in children. Pediatr. 2012;129:e1326–33. 10 Regev-Yochay G, Raz M, Dagan R, Roizin H, Morag B, Hetman S, et al. Reduction in antibiotic use following a cluster randomized controlled multifaceted intervention: The Israeli Judicious Antibiotic Prescription Study. Clin Infect Dis. 2011:53:33–41. 11 Falchi A, Lasserre A, Gallay A, Blanchon T, Sednaoui P, Lassau F, et al. A survey of primary care physician practices in antibiotic prescribing for the treatment of uncomplicated male gonoccocal urethritis. BMC Family Practice. 2011;12:35. 12 Cadieux G, Tamblyn R, Dauphinee D, Libman M. Predictors of inappropriate antibiotic prescribing among primary care physicians. Can Med Assoc J. 2007;177:877–83. 13 Hart J, Salman H, Bergman M, Neuman V, Rudniki C, Gilenberg D, et al. Do drug costs affect physicians’ prescription decisions? J Intern Med. 1997:241:415–20. 14 Watson RL, Dowell SF, Jayaraman M, Keyserling H, Kolczak M, Schwartz B. Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs. Pediatr. 1999;104;1251–7.
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Prescription of antibiotics and awareness of antibiotic costs by paediatricians in two hospitals in Greece Helena C. Maltezou1, Katerina Mougkou2, Elias Iosifidis3, Panos Katerelos1, Emmanuel Roilides3, Maria Theodoridou2 1
Department for Interventions in Health-Care Facilities, Hellenic Center for Diseases Control and Prevention, Athens, 21st Department of Pediatrics, University of Athens, ‘Aghia Sophia’ Children’s Hospital, Athens, 33rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration Hospital, Thessaloniki, Greece Our aim was to study the antibiotic prescription practices and the knowledge about antibiotic costs, brand and generic drugs of paediatricians working in two hospitals in Greece. The 2007 national guidelines were used as the gold standard for antibiotic prescription. A total of 126 paediatricians participated in the study (50.4% response rate). The mean compliance rate with the guidelines was 50.1% (range per infection: 10.6–84.7%). The mean scores of knowledge about antibiotic costs and about brand name and generic drugs were 35.6 and 60.3%, respectively. Linear regression analysis found a significant association between the mean compliance rate with the national guidelines and the paediatricians’ age (mean compliance rates were 49.1, 53.0, and 43.0% in the # 30, 31–40, and . 40 years age-groups, respectively; P 5 0.003). In conclusion, five years after the first national guidelines were issued in Greece only half of the paediatricians working in hospitals comply fully with them. Keywords: Antibiotics, Paediatrician, Hospital, Prescription, Cost
Introduction The use of antimicrobial agents in clinical practice in the second half of the twentieth century constituted a major achievement in medical history, leading to the prevention, treatment and control of several fearful infectious diseases of the past. However, the emergence and spread of antibiotic resistant or multiresistant pathogens globally in association with the unavailability of novel antibiotics is a public health threat.1,2 Unnecessary or inappropriate antibiotic use in the hospital setting and the community strongly contributes to the emergence of resistant pathogens. Thus, the limitation of unnecessary antibiotic use or misuse has become a public health priority globally.3,4 Greece is amongst the European countries with the highest rates of consumption of antibiotics and antibiotic resistance.5,6 Given this situation, the Hellenic Center for Diseases Control and Prevention (HCDCP) issued guidelines in 2007 in order to promote the rational use of antibiotics by physicians in hospitals and community settings. These guidelines were printed in pocket books and subsequently Correspondence to: Dr Helena C. Maltezou, Department for Interventions in Health-Care Facilities, Hellenic Center for Diseases Control and Prevention, 3-5 Agrafon Street, Athens, Greece. Email: helen-maltezou@ ath.forthnet.gr
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distributed to all hospital-based physicians. These guidelines are also available at the HCDCP website.7 Furthermore, the use of generic over brand name drugs is being promoted by the Ministry of Health the past two years, in order to reduce the health-associated expenditures within the current economic crisis. The aim of this study was to evaluate the antibiotic prescription practices for common infections among hospital-based paediatricians in Greece, using the HCDCP guidelines as the gold standard. The paediatricians’ knowledge about antibiotic costs, brand name and generic drugs was also studied.
Methods Primary objectives of the study were: (1) the estimation of the compliance of the paediatricians with the first recommended antibiotic; (2) the estimation of the compliance of the paediatricians with the first and the alternative recommended antibiotics; (3) the estimation of the knowledge of the paediatricians about antibiotic costs; and (4) the estimation of the knowledge of the paediatricians about brand and generic drugs. Secondary objectives were the investigation of any possible association of the abovementioned with the characteristics of the paediatricians.
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Figure 1 Antibiotic prescription practices and knowledge about antibiotics, brand name and generic drugs of hospital-based paediatricians
Two major hospitals were selected, Aghia Sophia Children’s Hospital in Athens (central/south Greece) and Hippokrateion General Hospital in Thessaloniki (north Greece), where a total of 292 paediatricians
are employed. During March 2012 a standardized questionnaire was distributed to 250 paediatricians (42 paediatricians were not available), irrespective of personal or professional characteristics (Fig. 1).
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Figure 1 Continued
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Paediatricians were asked to complete the questionnaire anonymously and return it within the next day. The completed questionnaires were sent to HCDCP for data entry and analysis. The following data were collected using one form per paediatrician: age, gender, hospital of practice, qualification(s) and year(s) of acquisition of qualification(s). In order to evaluate the paediatricians’ first-line empiric treatment choices, six scenarios for common infections in children were provided. In addition, there were six questions about the costs of common antibiotic regimens and five questions about brand name and generic drugs. The costs of common antibiotic regimens were estimated for a 20-kg child. A 95% confidence interval (CI) was computed for each of the four scores (finite population correction was applied since the total number of hospital paediatricians in Greece is approximately 1500) (Hellenic Statistical Authority; personal communication). Multiple linear regression (forward selection) was applied in order to identify which paediatricians characteristics (age and/or gender) are significantly associated with their compliance rates with the 2007 national guidelines. The following univariate tests were also used: t-test for gender and Pearson correlation coefficient for age. An association was regarded as reliable if it was traced by both the regression technique and the respective univariate test. The time (years) since the acquisition of the medical diploma and the time (years) since the acquisition of the paediatric specialty diploma were not included in the regression model due to missing values. Pearson correlation coefficient was applied to investigate the possible association between the rates of compliance with the national guidelines and the two knowledge scores. P values of 0.05 or less were considered statistically significant. The STATA 8.0 software was used for the statistical analysis software (StataCorp LP, College Station, TX, USA).
Results A total of 126 paediatricians participated in the study (50.4% response rate). Participants were mainly female (74.1%), had a mean age of 37.6 years (range: 27–66 years), had graduated from a medical school a mean of 15.7 years (range: 1–32 years) ago, and had completed their paediatric residency program a mean of 8.9 years (range: 1–41 years) ago. The paediatricians’ first choice for common infections and the antibiotics recommended for the respective infections in accordance with the 2007 national guidelines are depicted in Table 1. Compliance rates with the guidelines in terms of the first recommended antibiotic were 84.7% for bacterial skin infection, 71.4% for streptococcal pharyngitis, 65.9% for acute otitis media, 41.4% for bacterial
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pneumonia requiring admission in the hospital, 27.8% for bacterial community-acquired pneumonia, and 10.6% for urinary tract infection. Compliance rates with the guidelines using the first and the alternative recommended antibiotics as the gold standard was 100% for acute otitis media and bacterial pneumonia requiring hospitalization, 95.2% for bacterial skin infection, 84.1% for streptococcal pharyngitis, 53.2% for bacterial communityacquired pneumonia, and 58.5% for urinary tract infection. The highest variation in antibiotic prescription was noted in the scenario about a 9-year-old child with community-acquired pneumonia (nine antibiotics of whom six beyond the national guidelines). In terms of specific antibiotics, amoxicillin/ clavulanate (alone or in combination) was the most frequent antibiotic prescribed beyond the guidelines, accounting for 41.5, 36.5, and 14.3% of prescriptions for urinary tract infection, bacterial communityacquired pneumonia, and streptococcal pharyngitis, respectively. The overall mean compliance rate of paediatricians with the guidelines was 50.1% (standard deviation: 617.7; 47.2–53.1% 95% CIs) for the first recommended antibiotic and reached 82.0% (standard deviation: 613.5; 79.7–84.2% 95% CIs) when the first and the alterative recommended antibiotics were considered. In terms of the paediatricians’ knowledge about the cost of common antibiotic regimens in paediatrics, correct answers ranged from 27.9% for a 10-day regimen of clarithromycin to 79.4% for a 10-day regimen of penicillin V (Table 2). The overall mean score of knowledge about antibiotic costs was 35.6% (standard deviation: 617.9; 32.3–38.8% 95% CIs) Regarding the paediatricians’ knowledge about brand-name and generic drugs, correct answers ranged from 11.7 to 80%; the overall mean score of knowledge about brand name and generic drugs was 60.3% (standard deviation: 625.2; 56.1–64.6% 95% CIs). Linear regression analysis found a significant association between the mean compliance rate with the national guidelines in terms of the first antibiotic choice and the paediatricians’ age. In particular, the mean compliance rates with the first recommended antibiotic were 49.1, 53.0, and 43.0% in the # 30, 31–40, and . 40 years age-groups, respectively (linear regression P value 5 0.003/Pearson Correlation Coefficient 5 20.256, P value 5 0.007). No significant association between the paediatricians’ characteristics and their compliance rates with the first and the alternative recommended antibiotics was found, as well as between their characteristics and their knowledge scores about antibiotic costs, brand name drugs and generic drugs (data not shown). Lastly, a statistically significant association was found between the paediatricians’ compliance rate with the first recommended antibiotic
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Table 1 Antibiotic prescription by hospital-based paediatricians for common community-acquired infections n (%) Recommended antibiotic1
Infection/antibiotic a. Streptococcal pharyngitis Penicillin V Amoxicillin/clavulanate Amoxicillin Clarithromycin Other b. Bacterial CAP in a 9-year-old outpatient child Amoxicillin/clavulanate Clarithromycin Amoxicillin Amoxicillin/clavulanate & clarithromycin Amoxicillin & clarithromycin Penicillin V Cefuroxime Amoxicillin & cefuroxime Cefuroxime & clarithromycin Other c. Febrile UTI in a 2-year-old child Amoxicillin/clavulanate Cefuroxime Cefaclor Trimethoprim/sulphamethoxazole Amoxicillin Cefixime d. Bacterial skin infection Amoxicillin/clavulanate Clindamycin Penicillin V Macrolide Trimethoprim/sulphamethoxazole Other e. AOM in a 2-year-old child Amoxicillin Amoxicillin/clavulanate 2nd or 3rd generation cephalosporin Clarithromycin Other f. Bacterial pneumonia in a 3-year-old outpatient child Amoxicillin/clavulanate Ampicillin Cefuroxime Penicillin V Clarithromycin
1st choice
N 5 126
90 18 12 4 2
(71.4) (14.3) (9.5) (3.2) (1.6)
34 30 28 12 8 6 3 2 1 2
(27.0) (23.8) (22.2) (9.5) (6.3) (4.8) (2.4) (1.6) (0.8) (1.6)
51 27 18 13 10 4
(41.5) (22.0) (14.6) (10.6) (8.1) (3.3)
1st choice 1st choice Alternative choice Alternative choice
74 31 9 4 3 3
(59.7) (25.0) (7.3) (3.2) (2.4) (2.4)
1st choice Alternative choice Alternative choice
83 27 6 6 4
(65.9) (21.4) (4.8) (4.8) (3.2)
1st choice
52 43 19 10 2
(41.3) (34.1) (15.1) (7.9) (1.6)
Alternative choice Alternative choice
1st choice Alternative choice
1st choice Alternative choice alternative choice
Alternative Alternative 1st choice Alternative Alternative
choice choice choice choice
Alternative choice
Note: 1In accordance with the Hellenic Center for Disease Control and Prevention 2007 guidelines. CAP: community-acquired pneumonia; UTI: urinary tract infection; AOM: acute otitis media.
and the alternative recommended antibiotics (Pearson Correlation Coefficient 5 0.330, P value , 0.001). No association was found between the compliance rates with the guidelines and the two knowledge scores (about antibiotic costs and brand name and generic drugs), as well as between the two knowledge scores (data not shown).
Discussion The current study was conducted in order to record the antibiotic prescription practices by hospital-based paediatricians in Greece five years after the first national guidelines about the use of antibiotics were issued. To the best of our knowledge, only few similar studies have been published so far.8–10 Our study revealed gaps in antibiotic prescription, with only one every two hospital-based paediatricians complying
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fully with the guidelines in terms of first antibiotic choice. We found even lower compliance rates (37.4%) among private paediatricians in the same country (unpublished data). In the current study, compliance rates ranged widely depending on infectious indication, from as low as 10.6% for urinary tract infection to 84.7% for bacterial skin infection. Overall, amoxicillin/clavulanate, a broad-spectrum antibiotic, was the first choice for a wide range of indications. The low compliance with the national guidelines may be attributed to gaps in knowledge about the rational use of antibiotics, the paediatricians’ unfamiliarity with the guidelines, but also to difficulties to modify their perceptions and attitudes towards antibiotic use. In this study paediatricians older than 40 years of age were less likely to comply with the national
Maltezou et al.
Table 2 Knowledge of costs regimens by paediatricians Antibiotic/cost (Euros)*
for
common
antibiotic
Number of paediatricians (%)
Amoxicillin/clavulanate (50 mg/kg/d, tid for 10 days) (n 5 111) 5–10 24 (21.6) 11–20 59 (53.2) (correct) 21–30 28 (25.2) Clarithromycin (20 mg/kg/d, bid for 10 days) (n 5 111) 10–20 31 (27.9) (correct) 21–40 66 (59.5) 41–60 14 (12.6) Penicillin V (50 000 IU/kg/d, x4 for 10 days) (n 5 107) 5–15 85 (79.4) (correct) 16–25 20 (18.7) 26–35 2 (1.9) Trimethoprim/sulphamethoxazole (10 mg/kg/d, bid for 10 days) (n 5 110) 1–10 49 (44.5) (correct) 11–20 50 (45.5) 21–30 11 (10.0) Cefaclor (40 mg/kg/d, tid for 10 days) (n 5 109) 5–15 25 (22.9) 16–25 67 (61.5) (correct) 26–35 17 (15.6) Cefotaxime (150 mg/kg/d, tid for 10 days) (n 5 109) 50–100 36 (33.0) 101–200 37 (34.0) (correct) 201–300 36 (33.0) Note: *Estimated for a 20-kg child.
guidelines. This finding is in accordance with other studies showing that physicians in longer practice are more likely to prescribe antibiotics inappropriately.11,12 Courses about the rational antibiotic use and prescription behaviour have been incorporated in modern medical and residency curricula the past two decades, which may explain the abovementioned differences. In addition, in contrast to older physicians, younger physicians may use more frequently electronic sources, which may also contribute to the higher compliance rates with the national guidelines among the latter. The overall awareness of the costs of commonly prescribed antibiotic regimens was generally inadequate. It has been shown that information about costs may be an important factor in decision making and thus reduce health-care expenditures.13 We also found gaps in the paediatricians’ knowledge about brand name and generic drugs. Gaps in knowledge about brand name and generic drugs may limit the adoption of the latter by the medical community in this country. Our study had three potential limitations. Firstly, the participating paediatricians may not reflect precisely all hospital-based paediatricians in Greece. However, the precision of the mean values and the CIs of all our primary objectives studied were very high, indicating that the primary objectives were approached with a very high accuracy. Secondly, there are no prior data to compare the paediatricians’ prescription practices before and after the issuance of the 2007 guidelines. Thirdly, there is a possibility of
Antibiotic prescription in paediatrics
differentiation between the stated practices and realtime practice.14 However, our study provides information about the paediatricians’ antibiotic prescription practices and their knowledge about antibiotic costs. In conclusion, our study indicates that five years after the HCDCP issued the first national guidelines for antibiotic use in Greece, only half of the paediatricians working in two hospitals complied fully with them. Educational campaigns to promote the rational use of antibiotics by paediatricians and improve their prescription behaviour are warranted.
Acknowledgements We would like to thank the paediatricians for completing the questionnaires. We also thank Vasia Tsoutsa for technical assistance.
References 1 Maltezou HC. Metallo-b-lactamases in Gram-negative bacteria: introducing the era of pan-resistance? Int J Antimicrob Agent. 2009;33:405.e1–7. 2 French GL. The continuing crisis in antibiotic resistance. Int J Antimicrob Agent. 2010;3653:53–7. 3 World Health Organization. The evolving threat of antimicrobial resistance. Options for action. Geneva: WHO Press; 2012. 4 Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health. A public health action plan to combat antimicrobial resistance [document on the Internet]. [cited 2012 December 20]. Available from: http:// www.cdc.gov/drugresistance/pdf/public-health-action-plan-com bat-antimicrobial-resistance.pdf 5 European Surveillance of Antimicrobial Consumption. Consumption in Greece. [document on the Internet]. [cited 2012 December 20]. Available from: http://app.esac.ua.ac.be/ public/index.php/el_gr/antibiotic/in-your-country 6 European Centre for Disease Prevention and Control. European Antimicrobial Resistance Surveillance System Annual Reports. [document on the Internet]. [cited 2012 December 20]. Available from: http://ecdc.europa.eu/en/activities/ surveillance/EARS-Net/publications/Pages/documents.aspx 7 Hellenic Center for Disease Control and Prevention. Guidelines for the diagnosis and empiric treatment of infections, Athens 2007. [document on the Internet]. [cited 2012 December 20]. Available from: http://www.keelpno.gr/el-gr/diahe´simouliko´/ e´ntupouliko´.aspx [in Greek]. 8 Mckay RM, Vrbova L, Fuertes E, Chong M, David S, Dreher K, et al. Evaluation of the Do Bugs Need Drugs? Program in British Columbia: Can we curb antibiotic prescribing? Can J Infect Dis Med Microbiol. 2011;22:19–24. 9 Smith MJ, Kong M, Cambon A, Woods CR. Effectiveness of antimicrobial guidelines for community-acquired pneumonia in children. Pediatr. 2012;129:e1326–33. 10 Regev-Yochay G, Raz M, Dagan R, Roizin H, Morag B, Hetman S, et al. Reduction in antibiotic use following a cluster randomized controlled multifaceted intervention: The Israeli Judicious Antibiotic Prescription Study. Clin Infect Dis. 2011:53:33–41. 11 Falchi A, Lasserre A, Gallay A, Blanchon T, Sednaoui P, Lassau F, et al. A survey of primary care physician practices in antibiotic prescribing for the treatment of uncomplicated male gonoccocal urethritis. BMC Family Practice. 2011;12:35. 12 Cadieux G, Tamblyn R, Dauphinee D, Libman M. Predictors of inappropriate antibiotic prescribing among primary care physicians. Can Med Assoc J. 2007;177:877–83. 13 Hart J, Salman H, Bergman M, Neuman V, Rudniki C, Gilenberg D, et al. Do drug costs affect physicians’ prescription decisions? J Intern Med. 1997:241:415–20. 14 Watson RL, Dowell SF, Jayaraman M, Keyserling H, Kolczak M, Schwartz B. Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs. Pediatr. 1999;104;1251–7.
Journal of Chemotherapy
2014
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26
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