Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article
Use of antibiotics in paediatric primary care settings in Serbia Bojana Bozic,1 Milica Bajcetic1,2 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ archdischild-2015-308274). 1
Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia 2 Clinical Pharmacology Unit, University Children’s Hospital, Belgrade, Serbia
Drug therapy
Correspondence to Dr Bojana Bozic, Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, P.O. Box 38, Belgrade 11129, Serbia; [email protected] Received 20 January 2015 Revised 27 April 2015 Accepted 28 April 2015 Published Online First 20 May 2015
ABSTRACT Objective The aim of the study was to compare the quality of antibiotic use among children in primary settings with the internationally developed diseasespecific quality indicators and with National Guidelines. Design Prescriptions of systemic antibiotics to the paediatric population (25%).8 9 Studies published in the previous period showed
What is already known on this topic? ▸ Antibiotics are the most commonly prescribed drugs among the paediatric population. ▸ Extensive antibiotic use leads to the development of antibiotic-resistant infections, and also represents a significant economic burden.
What this study adds? Over 85% children in Serbia with a viral upper respiratory tract infection, tonsillitis or otitis media receive antibiotics. Inappropriate broad-spectrum antibiotics are usually prescribed. The irrational use of antibiotics in children in Serbia is a major problem.
great variations in antibiotic consumption between countries.9 The policy of no antibiotic prescribing or delayed prescribing is recommended in many European countries for conditions such as acute otitis media (AOM), acute sore throat/acute pharyngitis/acute tonsillitis, common cold, acute rhinosinusitis, acute cough and acute bronchitis.10 11 The European Surveillance Antimicrobial Consumption group (ESAC) has developed a set of 21 evidence-based disease-specific antibiotic prescribing quality indicators (APQI) for general primary care, of which 9 can be applied to the paediatric population.12 This set of indicators could be used for better description of antibiotic use and to assess the quality of national antibiotic prescription patterns in ambulatory care.12 13 The entire paediatric population up to 18 years of age in the Republic of Serbia (RS) has free mandatory health insurance coverage. The National Health Insurance Fund (NHIF) is responsible for financing the whole system of state-owned health centres, including the paediatrician-based system for primary care of children. Children up to the age of 6 who are treated in paediatric primary health settings, according to official norms, should have access to an ambulance within 15 min travel distance. Children between 7 and 18 years of age fall under paediatricians from primary health settings belonging to schools. The aim of the present study has been to evaluate antibiotic use among the outpatient paediatric population in Serbia for acute upper respiratory
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article tract infections, acute tonsillitis and AOM, with the internationally developed disease-specific quality indicators and National Guidelines.
MATERIALS AND METHODS
During the 3-year period studied, the average number of antibiotic prescriptions amounted to 1.887.615 (from 1.756.902 during 2012 to 2.072.519 during 2011) for the average 1.353.714 paediatric population in the RS. The average number of children receiving antibiotics was 728.285. The annual prevalence of antibiotics prescription decreased from 56% in 2011 to 53% in 2013. The prescription rate was slightly decreased by 10% from 1.516 antibiotic prescriptions per 1000 persons per year in 2011 to 1.365 in 2013. In all 3 years the highest prescription rates were among children in the age group from 2 to 23 months (figure 1). Acute upper respiratory infections (R74) 42%, acute tonsillitis (R76) 25% and AOM/myringitis (H71) 2% represented more than 69% of all indications for prescribing antibiotics. The most often prescribed antibiotics for acute respiratory infections and acute tonsillitis were amoxicillin (40%), cephalexin (21%), amoxicillin/clavulanic acid (18%) and azithromycin (12%). For AOM, the most often prescribed antibiotics were amoxicillin/ clavulanic acid (29%), cefixime (21%), amoxicillin (19%) and cefprozil (16%). There were no significant differences in nine evidence-based disease-specific quality indicators for outpatient antibiotic prescribing in children for the three diagnoses. The percentage of patients who received systemic antibiotics (indicator a) for acute upper respiratory tract infections, acute tonsillitis and AOM stayed significantly above the range proposed by the ESAC (table 2). For all three diseases, the percentage of children receiving the recommended antibiotics (indicator b) was significantly lower than the acceptable range proposed by the ESAC. The rate of adherence to our National Guidelines was at a low level during all 3 years. For acute upper respiratory tract infections and AOM, the adherence rate approached 28%, while for acute tonsillitis it was even lower at 19%. Quinolones use (indicator c) among the paediatric population in the RS for acute upper respiratory tract infections and for acute tonsillitis during the period studied was within the acceptable range (0.01%). The use of quinolones increased during the years for AOM, whereby in 2012 and 2013 it exceeded the acceptable range of 5%. There were no significant differences in indicators value at the regional level in Serbia (see online supplement 1).
DISCUSSION The RS, with an average annual rate of 1.394 prescriptions per 1000 children, appears to be one of the leading countries in antibiotic use.2 7 16–21 Only the findings from the study of Spain show a higher prescription rate (table 3).22
Table 1 Recommended antibiotics according to APQI and according to National Guidelines First choice antibiotics APQI
First choice antibiotics National Guidelines
Acute upper respiratory tract infections Acute tonsillitis
β-lactamase-sensitive penicillins
Acute otitis media
β-lactamase-sensitive penicillins or penicillins with extended spectrum
β-lactamase-sensitive penicillins or first-generation cephalosporins β-lactamase-sensitive penicillins or first-generation cephalosporins Penicillins with extended spectrum
Diagnosis
β-lactamase-sensitive penicillins
APQI, antibiotic prescribing quality indicators.
Figure 1 Prescription rates of systemic antibiotics per 1000 children per year stratified by age group.
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
967
Drug therapy
In a retrospective study, we analysed a set of the ESAC drugspecific quality indicators, which allowed us to estimate the use of antibiotics in certain diseases.12 13 The data were obtained from the NHIF outpatient reimbursement database between 2011 and 2013, for the outpatient population up to 18 years of age in the RS. The data obtained from the NHIF included all information about the insured children (age, indications and prescribed drugs). Out of 21 indicators, the ESAC proposed nine evidence-based disease-specific quality indicators for outpatient antibiotic prescribing in children: Indicator 2—acute upper respiratory infections (R74), Indicator 4—acute tonsillitis (R76) and Indicator 6—AOM/myringitis (H71), including three additional indicators for all three diagnoses: (a) the percentage of patients (>1 year for acute upper respiratory tract infections and tonsillitis; >2 years for AOM/myringitis) prescribed an antibiotic (acceptable range 0%–20%); (b) the percentage of patients (>1 year for acute upper respiratory tract infections and tonsillitis; >2 years for AOM/myringitis) having been prescribed an antibiotic, and receiving the guideline-recommended antibiotic (acceptable range 80%–100%); (c) the percentage of patients (>1 year for acute upper respiratory tract infections and tonsillitis; >2 years for AOM/myringitis) having been prescribed an antibiotic, and receiving quinolones (acceptable range 0%–5%).12 The methodology used to extract necessary data from the database and disease-specific APQI calculations are previously described by Adriaenssens et al.14 Specifically, we determined whether an antibiotic was prescribed when presenting for the first time. The recommended antibiotics were also analysed according to National Guidelines (table 1).15 The prescription rate, number of prescriptions divided by 1000 persons per year, was used as an indicator for describing the antibiotic prescription patterns. Indicators were calculated for the entire paediatric population in the RS, and also at the regional level: North region—Autonomous Province of Vojvodina (AP Vojvodina), South Serbia, and the capital region—Belgrade. The annual prevalence of antibiotic prescriptions was determined by using the average number of insured children during the respective years as the reference population.
RESULTS
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article Table 2 Disease-specific quality indicators for outpatient antibiotic prescribing for children in Serbia
Drug therapy
Indicators Values
Percentage of children prescribed an antibiotic
Percentage of children receiving recommended antibiotic
Percentage of children receiving a quinolone
ESAC suggested (%) Acute upper respiratory tract infections Acute tonsillitis Acute otitis media/myringitis
≤20 87 96 88
≥80 1 5 17
≤5 0 0 7
The high discrepancy in prescription rates among countries could be the consequence of social and cultural differences, incidence of community-acquired infections, awareness about rational antibiotic use and application of different regulations and guidelines for antibiotic use. The highest percentage of prescribed antibiotics was observed in the group of children 2 months to 23 months old, which is in accordance with the published evidence.7 18 22 23 Our study showed that more than one half of the paediatric population received at least one antibiotic prescription, which is much higher than in the UK, Netherlands or Germany (table 3).2 7 9 Our study showed that the percentage of children prescribed an antibiotic for acute respiratory tract infections, acute tonsillitis and AOM is more than 62% higher than the European consensus suggested from the ESAC. With respect to regional differences, irrational antibiotic use among children remains an urgent problem for all parts of the RS. In a study of Belgium practices, the percentage of adult and paediatric patients prescribed an antibiotic for acute respiratory tract infections was 32%–37%, for acute tonsillitis, 76%–84% and for AOM, 62%– 65%.14 Antibiotics are usually expected immediately in therapy, especially in cases of AOM, despite the policy of ‘watch and wait’.24 Similar findings were reported for German, US and Norwegian children.3 7 25 The high percentage of patients who received antibiotics indicates that inappropriate antibiotic use is a global phenomenon caused by the lack of a firm consensus on diagnosis and treatment for common infections among children.26–28 The extremely low percentage of Serbian children receiving the recommended antibiotic is a major finding for concern. The most often prescribed antibiotics for acute respiratory tract infections and acute tonsillitis were amoxicillin, amoxicillin/clavulanic acid, cephalexin and azithromycin, which are not in concordance with the APQI.12
The high percentage of patients (up to 68%) who received amoxicillin and amoxicillin/clavulanic acid in the treatment of tonsillopharyngitis are indications that the precise instructions issued by National Guidelines to avoid these antibiotics are not being followed.15 Similar recommendations are being issued in Sweden where, according to the STRAMA programme, it is not justified to use ampicillin derivatives (ampicillin/amoxicillin/ co-amoxiclav) in cases of tonsillopharyngitis because of the higher incidence of adverse effects and resistance development.29 However, even though narrow-spectrum penicillins are recommended for these infections,12 15 they are often unavailable in Serbia, owing to the lack of interest of pharmaceutical companies due to insufficient economic benefits. One of the most alarming results concerning treatment of acute upper respiratory infections and acute tonsillitis is the use of azithromycin in a high percentage of cases (up to 13.7%), which is in line with the findings for the Netherlands, Italy and Germany also.2 7 26 The high consumption of macrolides leads to increased resistance of Streptococcus pyogenes and S. pneumonia, in the paediatric population.30 In our study, 72% of patients treated for AOM received either amoxicillin/clavulanic acid or cephalosporins of II and III generations, which are all designated as alternative antibiotics according to National Guidelines.15 Amoxicillin, marked as the first choice treatment for AOM according to Italian, National Institute of Health and Care Excellence (NICE), APQI and our own National Guidelines, came only third on the list of the most prescribed antibiotics for AOM.10 12 15 31 32 A study conducted in the USA from 2000–2011 that followed trends in antibiotic treatment for AOM showed an unjustifiably high use of cephalosporins as initial therapy.33 In France, in order to decrease indications for antibiotic use, The French National Agency for Medicines and Health Products Safety made new recommendations to simplify the antibiotic therapy scheme,
Table 3 Prescription rate and prevalence in published studies evaluating antibiotic prescription Reference
Period
Country
Number of prescriptions/ 1000 children/year
Annual prevalence
2 16 17 18 9, 19 16 20 7 9, 21 7, 9 22
2004 2007 2003 2003 1999/2000; 2007 2007 2009 2006 1999/2001; 2000 2002; 2006 2004/2005
Netherlands Sweden Denmark Canada UK Estonia Ireland Germany USA Italy Spain
282 353 385 488 568 616 621 708 910 1151 1581
18% NR NR NR 14% NR NR 38% 28% 52% NR
NR, not reported.
968
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article
Contributors BB in collaboration with MB processed data, made tables and figures and wrote the paper; MB designed the study and wrote the paper. Funding Supported by the Ministry of Education and Science of the Republic of Serbia grant number OI173014. Competing interests MB was Director of the Department of Medicine and Pharmacoeconomics at the National Health Insurance Fund of Serbia until January 2015. Provenance and peer review Not commissioned; externally peer reviewed.
9 10
11 12
13
14
15
16 17 18 19
20 21
22
23
24 25
26
27 28
29
REFERENCES 1
2 3 4 5
6 7 8
Pulcini C, Lions C, Ventelou B, et al. Indicators show differences in antibiotic use between general practitioners and paediatricians. Eur J Clin Microbiol Infect Dis 2013;32:929–35. de Jong J, van den Berg PB, de Vries TW, et al. Antibiotic drug use of children in the Netherlands from 1999 till 2005. Eur J Clin Pharmacol 2008;64:913–19. Hersh AL, Shapiro DJ, Pavia AT, et al. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics 2011;128:1053–61. Regoli M, Chiappini E, Bonsignori F, et al. Update on the management of acute pharyngitis in children. Ital J Pediatr 2011;37:10. Hersh AL, Jackson MA, Hicks LA., American Academy of Pediatrics Committee on Infectious Diseases. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics 2013;132:1146–54. Abzug MJ. Acute sinusitis in children: do antibiotics have any role? J Infect 2014;68 (Suppl 1):S33–7. Holstiege J, Garbe E. Systemic antibiotic use among children and adolescents in Germany: a population-based study. Eur J Pediatr 2013;172:787–95. Jacobs MR. Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children. Pediatr Infect Dis J 2003;22:109–19.
30
31
32
33 34 35 36
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
Clavenna A, Bonati M. Differences in antibiotic prescribing in paediatric outpatients. Arch Dis Child 2011;96:590–5. NICE Short Clinical Guidelines Technical Team Respiratory tract infections–antibiotic prescribing. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. London, National Institute for Health and Clinical Excellence, 2008. Van Brusselen D, Vlieghe E, Schelstraete P, et al. Streptococcal pharyngitis in children: to treat or not to treat? Eur J Pediatr 2014;173:1275–83. Adriaenssens N, Coenen S, Tonkin-Crine S, et al, ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): disease-specific quality indicators for outpatient antibiotic prescribing. BMJ Qual Saf 2011;20:764–72. Coenen S, Ferech M, Haaijer-Ruskamp FM, et al, ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for outpatient antibiotic use in Europe. Qual Saf Health Care 2007;16:440–5. Adriaenssens N, Bartholomeeusen S, Ryckebosch P, et al. Quality of antibiotic prescription during office hours and out-of-hours in Flemish primary care, using European quality indicators. Eur J Gen Pract 2014;20:114–20. The choice and consumption of antibiotic in primary practice. Nacionalni vodič za lekare u primarnoj zdravstvenoj zaštiti. 2004. http://www.zdravlje.gov.rs/downloads/ 2008/Sa%20Zdravlja/dokumenta/Vodici/ANTIBIOTICI%20u%20opstoj%20praksi.pdf (accessed Nov 2013). Lass J, Odlind V, Irs A, et al. Antibiotic prescription preferences in paediatric outpatient setting in Estonia and Sweden. Springer Plus 2013;2:124. Marra F, Monnet DL, Patrick DM, et al. A comparison of antibiotic use in children between Canada and Denmark. Ann Pharmacother 2007;41:659–66. Marra F, Patrick D, Chong M, et al. Antibiotic use among children in British Columbia, Canada. J Antimicrob Chemother 2006;58:830–9. Schneider-Lindner V, Quach C, Hanley JA, et al. Secular trends of antibacterial prescribing in UK paediatric primary care. J Antimicrob Chemother 2011;66:424–33. Keogh C, Motterlini N, Reulbach U, et al. Antibiotic prescribing trends in a paediatric sub-population in Ireland. Pharmacoepidemiol Drug Saf 2012;21:945–52. Stille CJ, Andrade SE, Huang SS, et al. Increased use of second-generation macrolide antibiotics for children in nine health plans in the United States. Pediatrics 2004;114:1206–11. Sharland M, SACAR Paediatric Subgroup. The use of antibacterials in children: a report of the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) Paediatric Subgroup. J Antimicrob Chemother 2007;60:15–26. Rossignoli A, Clavenna A, Bonati M. Antibiotic prescription and prevalence rate in the outpatient paediatric population: analysis of surveys published during 2000– 2005. Eur J Clin Pharmacol 2007;63:1099–106. Barber C, Ille S, Vergison A, et al. Acute otitis media in young children—What do parents say? Int J Pediatr Otorhinolaryngol 2014;78:300–6. Fossum GH, Lindbaeæk M, Gjelstad S, et al. Are children carrying the burden of broad-spectrum antibiotics in general practice? Prescription pattern for paediatric outpatients with respiratory tract infections in Norway. BMJ Open 2013;3:e002285. Piovani D, Clavenna A, Cartabia M, et al., Antibiotic Collaborative Group. The regional profile of antibiotic prescriptions in Italian outpatient children. Eur J Clin Pharmacol 2012;68:997–1005. Cartabia M, Campi R, Clavenna A, et al. Geographical epidemiology of antibacterials in the preschool age. Int J Health Geogr 2012;11:52. Clavenna A, Sequi M, Bonati M. Differences in the drug prescriptions to children by Italian paediatricians and general practitioners. Eur J Clin Pharmacol 2010;66:519–24. STRAMA. The Swedish Strategic Programme for the Rational use of Antimicrobial Agents. Swedish guidelines for the treatment of rhinosinusitis, pharyngotonsillitis and acute otitis media in children. http://www.strama.se Mijac V, Opavski N, Markovic M, et al. Trends in macrolide resistance of respiratory tract pathogens in the paediatric population in Serbia from 2004 to 2009. Epidemiol Infect 2015;143:648–52. Marchisio P, Bellussi L, Di Mauro G, et al. Acute otitis media: From diagnosis to prevention. Summary of the Italian guideline. Int J Pediatr Otorhinolaryngol 2010;74:1209–16. Chiappini E, Mazzantini R, Bruzzese E, et al. Rational use of antibiotics for the management of children’s respiratory tract infections in the ambulatory setting: an evidence-based consensus by the Italian Society of Preventive and Social Pediatrics. Paediatr Respir Rev 2014;15:231–6. McGrath LJ, Becker-Dreps S, Pate V, et al. Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000–2011. PLos ONE 2013;8:12. Levy C, Pereira M, Guedj R, et al. Impact of 2011 French guidelines on antibiotic prescription for acute otitis media in infants. Med Mal Infect 2014;44:102–6. Coco AS. Cost-effectiveness analysis of treatment options for acute otitis media. Ann Fam Med 2007;5:29–38. Leibovitz E. The use of fluoroquinolones in children. Curr Opin Pediatr 2006;18:64–70.
969
Drug therapy
which led to concrete results. In France, during 2012 the amount of amoxicillin prescribed increased compared with the amount of amoxicillin/clavulanic acid or cefpodoxime for the treatment of AOM in children.34 Differences in treatment for AOM exist between guidelines not only with respect to recommended antibiotic class. The majority of guidelines advise antibiotic use only in cases of severe symptoms at the first examination or in children under the age of 2 years.7 10 The information that was available for our study did not include data on severity and duration of symptoms, so a further comparison at this level could not be performed. Although all the costs and consequences of increasing antibiotic use among children for AOM cannot be measured, studies have shown that delayed prescription would significantly reduce healthcare system expenses and lessen the resistance to antibiotics.35 Quinolones are contraindicated in young children and the only justifiable indications for their use are life-threatening conditions.36 Data published from Belgium showed that the percentage of patients who received quinolones for acute respiratory tract infections and acute tonsillitis is around 3%, which is higher than the values obtained from our study.14 However, our results for AOM quinolones treatment are above the suggested ESAC range and require special attention. On the basis of all the results, we may conclude that the policy of appropriate antibiotic use has not been executed effectively in the paediatric population so far. Prescribing antibiotics in cases where there are no clear indications for their use, and also the frequent use of broad-spectrum antibiotics, are major problems that go back many years. All of these findings provide grounds for reasonable concern, and point to the need for a specifically created guideline for the paediatric population. For all the reasons mentioned, great efforts must be made to encourage the rationalisation of antimicrobial therapy, and also to raise awareness about the global consequences of inappropriate antibiotic exposure.
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Use of antibiotics in paediatric primary care settings in Serbia Bojana Bozic and Milica Bajcetic Arch Dis Child 2015 100: 966-969 originally published online May 20, 2015
doi: 10.1136/archdischild-2015-308274 Updated information and services can be found at: http://adc.bmj.com/content/100/10/966
These include:
Supplementary Supplementary material can be found at: Material http://adc.bmj.com/content/suppl/2015/05/19/archdischild-2015-3082 74.DC1.html
References Email alerting service
Topic Collections
This article cites 33 articles, 11 of which you can access for free at: http://adc.bmj.com/content/100/10/966#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections ADC Drug Therapy (116) Drugs: infectious diseases (892) Child health (3661) Health policy (176) Otitis (63) TB and other respiratory infections (611)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Original article
Use of antibiotics in paediatric primary care settings in Serbia Bojana Bozic,1 Milica Bajcetic1,2 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ archdischild-2015-308274). 1
Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia 2 Clinical Pharmacology Unit, University Children’s Hospital, Belgrade, Serbia
Drug therapy
Correspondence to Dr Bojana Bozic, Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, P.O. Box 38, Belgrade 11129, Serbia; [email protected] Received 20 January 2015 Revised 27 April 2015 Accepted 28 April 2015 Published Online First 20 May 2015
ABSTRACT Objective The aim of the study was to compare the quality of antibiotic use among children in primary settings with the internationally developed diseasespecific quality indicators and with National Guidelines. Design Prescriptions of systemic antibiotics to the paediatric population (25%).8 9 Studies published in the previous period showed
What is already known on this topic? ▸ Antibiotics are the most commonly prescribed drugs among the paediatric population. ▸ Extensive antibiotic use leads to the development of antibiotic-resistant infections, and also represents a significant economic burden.
What this study adds? Over 85% children in Serbia with a viral upper respiratory tract infection, tonsillitis or otitis media receive antibiotics. Inappropriate broad-spectrum antibiotics are usually prescribed. The irrational use of antibiotics in children in Serbia is a major problem.
great variations in antibiotic consumption between countries.9 The policy of no antibiotic prescribing or delayed prescribing is recommended in many European countries for conditions such as acute otitis media (AOM), acute sore throat/acute pharyngitis/acute tonsillitis, common cold, acute rhinosinusitis, acute cough and acute bronchitis.10 11 The European Surveillance Antimicrobial Consumption group (ESAC) has developed a set of 21 evidence-based disease-specific antibiotic prescribing quality indicators (APQI) for general primary care, of which 9 can be applied to the paediatric population.12 This set of indicators could be used for better description of antibiotic use and to assess the quality of national antibiotic prescription patterns in ambulatory care.12 13 The entire paediatric population up to 18 years of age in the Republic of Serbia (RS) has free mandatory health insurance coverage. The National Health Insurance Fund (NHIF) is responsible for financing the whole system of state-owned health centres, including the paediatrician-based system for primary care of children. Children up to the age of 6 who are treated in paediatric primary health settings, according to official norms, should have access to an ambulance within 15 min travel distance. Children between 7 and 18 years of age fall under paediatricians from primary health settings belonging to schools. The aim of the present study has been to evaluate antibiotic use among the outpatient paediatric population in Serbia for acute upper respiratory
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article tract infections, acute tonsillitis and AOM, with the internationally developed disease-specific quality indicators and National Guidelines.
MATERIALS AND METHODS
During the 3-year period studied, the average number of antibiotic prescriptions amounted to 1.887.615 (from 1.756.902 during 2012 to 2.072.519 during 2011) for the average 1.353.714 paediatric population in the RS. The average number of children receiving antibiotics was 728.285. The annual prevalence of antibiotics prescription decreased from 56% in 2011 to 53% in 2013. The prescription rate was slightly decreased by 10% from 1.516 antibiotic prescriptions per 1000 persons per year in 2011 to 1.365 in 2013. In all 3 years the highest prescription rates were among children in the age group from 2 to 23 months (figure 1). Acute upper respiratory infections (R74) 42%, acute tonsillitis (R76) 25% and AOM/myringitis (H71) 2% represented more than 69% of all indications for prescribing antibiotics. The most often prescribed antibiotics for acute respiratory infections and acute tonsillitis were amoxicillin (40%), cephalexin (21%), amoxicillin/clavulanic acid (18%) and azithromycin (12%). For AOM, the most often prescribed antibiotics were amoxicillin/ clavulanic acid (29%), cefixime (21%), amoxicillin (19%) and cefprozil (16%). There were no significant differences in nine evidence-based disease-specific quality indicators for outpatient antibiotic prescribing in children for the three diagnoses. The percentage of patients who received systemic antibiotics (indicator a) for acute upper respiratory tract infections, acute tonsillitis and AOM stayed significantly above the range proposed by the ESAC (table 2). For all three diseases, the percentage of children receiving the recommended antibiotics (indicator b) was significantly lower than the acceptable range proposed by the ESAC. The rate of adherence to our National Guidelines was at a low level during all 3 years. For acute upper respiratory tract infections and AOM, the adherence rate approached 28%, while for acute tonsillitis it was even lower at 19%. Quinolones use (indicator c) among the paediatric population in the RS for acute upper respiratory tract infections and for acute tonsillitis during the period studied was within the acceptable range (0.01%). The use of quinolones increased during the years for AOM, whereby in 2012 and 2013 it exceeded the acceptable range of 5%. There were no significant differences in indicators value at the regional level in Serbia (see online supplement 1).
DISCUSSION The RS, with an average annual rate of 1.394 prescriptions per 1000 children, appears to be one of the leading countries in antibiotic use.2 7 16–21 Only the findings from the study of Spain show a higher prescription rate (table 3).22
Table 1 Recommended antibiotics according to APQI and according to National Guidelines First choice antibiotics APQI
First choice antibiotics National Guidelines
Acute upper respiratory tract infections Acute tonsillitis
β-lactamase-sensitive penicillins
Acute otitis media
β-lactamase-sensitive penicillins or penicillins with extended spectrum
β-lactamase-sensitive penicillins or first-generation cephalosporins β-lactamase-sensitive penicillins or first-generation cephalosporins Penicillins with extended spectrum
Diagnosis
β-lactamase-sensitive penicillins
APQI, antibiotic prescribing quality indicators.
Figure 1 Prescription rates of systemic antibiotics per 1000 children per year stratified by age group.
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
967
Drug therapy
In a retrospective study, we analysed a set of the ESAC drugspecific quality indicators, which allowed us to estimate the use of antibiotics in certain diseases.12 13 The data were obtained from the NHIF outpatient reimbursement database between 2011 and 2013, for the outpatient population up to 18 years of age in the RS. The data obtained from the NHIF included all information about the insured children (age, indications and prescribed drugs). Out of 21 indicators, the ESAC proposed nine evidence-based disease-specific quality indicators for outpatient antibiotic prescribing in children: Indicator 2—acute upper respiratory infections (R74), Indicator 4—acute tonsillitis (R76) and Indicator 6—AOM/myringitis (H71), including three additional indicators for all three diagnoses: (a) the percentage of patients (>1 year for acute upper respiratory tract infections and tonsillitis; >2 years for AOM/myringitis) prescribed an antibiotic (acceptable range 0%–20%); (b) the percentage of patients (>1 year for acute upper respiratory tract infections and tonsillitis; >2 years for AOM/myringitis) having been prescribed an antibiotic, and receiving the guideline-recommended antibiotic (acceptable range 80%–100%); (c) the percentage of patients (>1 year for acute upper respiratory tract infections and tonsillitis; >2 years for AOM/myringitis) having been prescribed an antibiotic, and receiving quinolones (acceptable range 0%–5%).12 The methodology used to extract necessary data from the database and disease-specific APQI calculations are previously described by Adriaenssens et al.14 Specifically, we determined whether an antibiotic was prescribed when presenting for the first time. The recommended antibiotics were also analysed according to National Guidelines (table 1).15 The prescription rate, number of prescriptions divided by 1000 persons per year, was used as an indicator for describing the antibiotic prescription patterns. Indicators were calculated for the entire paediatric population in the RS, and also at the regional level: North region—Autonomous Province of Vojvodina (AP Vojvodina), South Serbia, and the capital region—Belgrade. The annual prevalence of antibiotic prescriptions was determined by using the average number of insured children during the respective years as the reference population.
RESULTS
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article Table 2 Disease-specific quality indicators for outpatient antibiotic prescribing for children in Serbia
Drug therapy
Indicators Values
Percentage of children prescribed an antibiotic
Percentage of children receiving recommended antibiotic
Percentage of children receiving a quinolone
ESAC suggested (%) Acute upper respiratory tract infections Acute tonsillitis Acute otitis media/myringitis
≤20 87 96 88
≥80 1 5 17
≤5 0 0 7
The high discrepancy in prescription rates among countries could be the consequence of social and cultural differences, incidence of community-acquired infections, awareness about rational antibiotic use and application of different regulations and guidelines for antibiotic use. The highest percentage of prescribed antibiotics was observed in the group of children 2 months to 23 months old, which is in accordance with the published evidence.7 18 22 23 Our study showed that more than one half of the paediatric population received at least one antibiotic prescription, which is much higher than in the UK, Netherlands or Germany (table 3).2 7 9 Our study showed that the percentage of children prescribed an antibiotic for acute respiratory tract infections, acute tonsillitis and AOM is more than 62% higher than the European consensus suggested from the ESAC. With respect to regional differences, irrational antibiotic use among children remains an urgent problem for all parts of the RS. In a study of Belgium practices, the percentage of adult and paediatric patients prescribed an antibiotic for acute respiratory tract infections was 32%–37%, for acute tonsillitis, 76%–84% and for AOM, 62%– 65%.14 Antibiotics are usually expected immediately in therapy, especially in cases of AOM, despite the policy of ‘watch and wait’.24 Similar findings were reported for German, US and Norwegian children.3 7 25 The high percentage of patients who received antibiotics indicates that inappropriate antibiotic use is a global phenomenon caused by the lack of a firm consensus on diagnosis and treatment for common infections among children.26–28 The extremely low percentage of Serbian children receiving the recommended antibiotic is a major finding for concern. The most often prescribed antibiotics for acute respiratory tract infections and acute tonsillitis were amoxicillin, amoxicillin/clavulanic acid, cephalexin and azithromycin, which are not in concordance with the APQI.12
The high percentage of patients (up to 68%) who received amoxicillin and amoxicillin/clavulanic acid in the treatment of tonsillopharyngitis are indications that the precise instructions issued by National Guidelines to avoid these antibiotics are not being followed.15 Similar recommendations are being issued in Sweden where, according to the STRAMA programme, it is not justified to use ampicillin derivatives (ampicillin/amoxicillin/ co-amoxiclav) in cases of tonsillopharyngitis because of the higher incidence of adverse effects and resistance development.29 However, even though narrow-spectrum penicillins are recommended for these infections,12 15 they are often unavailable in Serbia, owing to the lack of interest of pharmaceutical companies due to insufficient economic benefits. One of the most alarming results concerning treatment of acute upper respiratory infections and acute tonsillitis is the use of azithromycin in a high percentage of cases (up to 13.7%), which is in line with the findings for the Netherlands, Italy and Germany also.2 7 26 The high consumption of macrolides leads to increased resistance of Streptococcus pyogenes and S. pneumonia, in the paediatric population.30 In our study, 72% of patients treated for AOM received either amoxicillin/clavulanic acid or cephalosporins of II and III generations, which are all designated as alternative antibiotics according to National Guidelines.15 Amoxicillin, marked as the first choice treatment for AOM according to Italian, National Institute of Health and Care Excellence (NICE), APQI and our own National Guidelines, came only third on the list of the most prescribed antibiotics for AOM.10 12 15 31 32 A study conducted in the USA from 2000–2011 that followed trends in antibiotic treatment for AOM showed an unjustifiably high use of cephalosporins as initial therapy.33 In France, in order to decrease indications for antibiotic use, The French National Agency for Medicines and Health Products Safety made new recommendations to simplify the antibiotic therapy scheme,
Table 3 Prescription rate and prevalence in published studies evaluating antibiotic prescription Reference
Period
Country
Number of prescriptions/ 1000 children/year
Annual prevalence
2 16 17 18 9, 19 16 20 7 9, 21 7, 9 22
2004 2007 2003 2003 1999/2000; 2007 2007 2009 2006 1999/2001; 2000 2002; 2006 2004/2005
Netherlands Sweden Denmark Canada UK Estonia Ireland Germany USA Italy Spain
282 353 385 488 568 616 621 708 910 1151 1581
18% NR NR NR 14% NR NR 38% 28% 52% NR
NR, not reported.
968
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Original article
Contributors BB in collaboration with MB processed data, made tables and figures and wrote the paper; MB designed the study and wrote the paper. Funding Supported by the Ministry of Education and Science of the Republic of Serbia grant number OI173014. Competing interests MB was Director of the Department of Medicine and Pharmacoeconomics at the National Health Insurance Fund of Serbia until January 2015. Provenance and peer review Not commissioned; externally peer reviewed.
9 10
11 12
13
14
15
16 17 18 19
20 21
22
23
24 25
26
27 28
29
REFERENCES 1
2 3 4 5
6 7 8
Pulcini C, Lions C, Ventelou B, et al. Indicators show differences in antibiotic use between general practitioners and paediatricians. Eur J Clin Microbiol Infect Dis 2013;32:929–35. de Jong J, van den Berg PB, de Vries TW, et al. Antibiotic drug use of children in the Netherlands from 1999 till 2005. Eur J Clin Pharmacol 2008;64:913–19. Hersh AL, Shapiro DJ, Pavia AT, et al. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics 2011;128:1053–61. Regoli M, Chiappini E, Bonsignori F, et al. Update on the management of acute pharyngitis in children. Ital J Pediatr 2011;37:10. Hersh AL, Jackson MA, Hicks LA., American Academy of Pediatrics Committee on Infectious Diseases. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics 2013;132:1146–54. Abzug MJ. Acute sinusitis in children: do antibiotics have any role? J Infect 2014;68 (Suppl 1):S33–7. Holstiege J, Garbe E. Systemic antibiotic use among children and adolescents in Germany: a population-based study. Eur J Pediatr 2013;172:787–95. Jacobs MR. Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children. Pediatr Infect Dis J 2003;22:109–19.
30
31
32
33 34 35 36
Bozic B, Bajcetic M. Arch Dis Child 2015;100:966–969. doi:10.1136/archdischild-2015-308274
Clavenna A, Bonati M. Differences in antibiotic prescribing in paediatric outpatients. Arch Dis Child 2011;96:590–5. NICE Short Clinical Guidelines Technical Team Respiratory tract infections–antibiotic prescribing. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. London, National Institute for Health and Clinical Excellence, 2008. Van Brusselen D, Vlieghe E, Schelstraete P, et al. Streptococcal pharyngitis in children: to treat or not to treat? Eur J Pediatr 2014;173:1275–83. Adriaenssens N, Coenen S, Tonkin-Crine S, et al, ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): disease-specific quality indicators for outpatient antibiotic prescribing. BMJ Qual Saf 2011;20:764–72. Coenen S, Ferech M, Haaijer-Ruskamp FM, et al, ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for outpatient antibiotic use in Europe. Qual Saf Health Care 2007;16:440–5. Adriaenssens N, Bartholomeeusen S, Ryckebosch P, et al. Quality of antibiotic prescription during office hours and out-of-hours in Flemish primary care, using European quality indicators. Eur J Gen Pract 2014;20:114–20. The choice and consumption of antibiotic in primary practice. Nacionalni vodič za lekare u primarnoj zdravstvenoj zaštiti. 2004. http://www.zdravlje.gov.rs/downloads/ 2008/Sa%20Zdravlja/dokumenta/Vodici/ANTIBIOTICI%20u%20opstoj%20praksi.pdf (accessed Nov 2013). Lass J, Odlind V, Irs A, et al. Antibiotic prescription preferences in paediatric outpatient setting in Estonia and Sweden. Springer Plus 2013;2:124. Marra F, Monnet DL, Patrick DM, et al. A comparison of antibiotic use in children between Canada and Denmark. Ann Pharmacother 2007;41:659–66. Marra F, Patrick D, Chong M, et al. Antibiotic use among children in British Columbia, Canada. J Antimicrob Chemother 2006;58:830–9. Schneider-Lindner V, Quach C, Hanley JA, et al. Secular trends of antibacterial prescribing in UK paediatric primary care. J Antimicrob Chemother 2011;66:424–33. Keogh C, Motterlini N, Reulbach U, et al. Antibiotic prescribing trends in a paediatric sub-population in Ireland. Pharmacoepidemiol Drug Saf 2012;21:945–52. Stille CJ, Andrade SE, Huang SS, et al. Increased use of second-generation macrolide antibiotics for children in nine health plans in the United States. Pediatrics 2004;114:1206–11. Sharland M, SACAR Paediatric Subgroup. The use of antibacterials in children: a report of the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) Paediatric Subgroup. J Antimicrob Chemother 2007;60:15–26. Rossignoli A, Clavenna A, Bonati M. Antibiotic prescription and prevalence rate in the outpatient paediatric population: analysis of surveys published during 2000– 2005. Eur J Clin Pharmacol 2007;63:1099–106. Barber C, Ille S, Vergison A, et al. Acute otitis media in young children—What do parents say? Int J Pediatr Otorhinolaryngol 2014;78:300–6. Fossum GH, Lindbaeæk M, Gjelstad S, et al. Are children carrying the burden of broad-spectrum antibiotics in general practice? Prescription pattern for paediatric outpatients with respiratory tract infections in Norway. BMJ Open 2013;3:e002285. Piovani D, Clavenna A, Cartabia M, et al., Antibiotic Collaborative Group. The regional profile of antibiotic prescriptions in Italian outpatient children. Eur J Clin Pharmacol 2012;68:997–1005. Cartabia M, Campi R, Clavenna A, et al. Geographical epidemiology of antibacterials in the preschool age. Int J Health Geogr 2012;11:52. Clavenna A, Sequi M, Bonati M. Differences in the drug prescriptions to children by Italian paediatricians and general practitioners. Eur J Clin Pharmacol 2010;66:519–24. STRAMA. The Swedish Strategic Programme for the Rational use of Antimicrobial Agents. Swedish guidelines for the treatment of rhinosinusitis, pharyngotonsillitis and acute otitis media in children. http://www.strama.se Mijac V, Opavski N, Markovic M, et al. Trends in macrolide resistance of respiratory tract pathogens in the paediatric population in Serbia from 2004 to 2009. Epidemiol Infect 2015;143:648–52. Marchisio P, Bellussi L, Di Mauro G, et al. Acute otitis media: From diagnosis to prevention. Summary of the Italian guideline. Int J Pediatr Otorhinolaryngol 2010;74:1209–16. Chiappini E, Mazzantini R, Bruzzese E, et al. Rational use of antibiotics for the management of children’s respiratory tract infections in the ambulatory setting: an evidence-based consensus by the Italian Society of Preventive and Social Pediatrics. Paediatr Respir Rev 2014;15:231–6. McGrath LJ, Becker-Dreps S, Pate V, et al. Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000–2011. PLos ONE 2013;8:12. Levy C, Pereira M, Guedj R, et al. Impact of 2011 French guidelines on antibiotic prescription for acute otitis media in infants. Med Mal Infect 2014;44:102–6. Coco AS. Cost-effectiveness analysis of treatment options for acute otitis media. Ann Fam Med 2007;5:29–38. Leibovitz E. The use of fluoroquinolones in children. Curr Opin Pediatr 2006;18:64–70.
969
Drug therapy
which led to concrete results. In France, during 2012 the amount of amoxicillin prescribed increased compared with the amount of amoxicillin/clavulanic acid or cefpodoxime for the treatment of AOM in children.34 Differences in treatment for AOM exist between guidelines not only with respect to recommended antibiotic class. The majority of guidelines advise antibiotic use only in cases of severe symptoms at the first examination or in children under the age of 2 years.7 10 The information that was available for our study did not include data on severity and duration of symptoms, so a further comparison at this level could not be performed. Although all the costs and consequences of increasing antibiotic use among children for AOM cannot be measured, studies have shown that delayed prescription would significantly reduce healthcare system expenses and lessen the resistance to antibiotics.35 Quinolones are contraindicated in young children and the only justifiable indications for their use are life-threatening conditions.36 Data published from Belgium showed that the percentage of patients who received quinolones for acute respiratory tract infections and acute tonsillitis is around 3%, which is higher than the values obtained from our study.14 However, our results for AOM quinolones treatment are above the suggested ESAC range and require special attention. On the basis of all the results, we may conclude that the policy of appropriate antibiotic use has not been executed effectively in the paediatric population so far. Prescribing antibiotics in cases where there are no clear indications for their use, and also the frequent use of broad-spectrum antibiotics, are major problems that go back many years. All of these findings provide grounds for reasonable concern, and point to the need for a specifically created guideline for the paediatric population. For all the reasons mentioned, great efforts must be made to encourage the rationalisation of antimicrobial therapy, and also to raise awareness about the global consequences of inappropriate antibiotic exposure.
Downloaded from http://adc.bmj.com/ on September 23, 2015 - Published by group.bmj.com
Use of antibiotics in paediatric primary care settings in Serbia Bojana Bozic and Milica Bajcetic Arch Dis Child 2015 100: 966-969 originally published online May 20, 2015
doi: 10.1136/archdischild-2015-308274 Updated information and services can be found at: http://adc.bmj.com/content/100/10/966
These include:
Supplementary Supplementary material can be found at: Material http://adc.bmj.com/content/suppl/2015/05/19/archdischild-2015-3082 74.DC1.html
References Email alerting service
Topic Collections
This article cites 33 articles, 11 of which you can access for free at: http://adc.bmj.com/content/100/10/966#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections ADC Drug Therapy (116) Drugs: infectious diseases (892) Child health (3661) Health policy (176) Otitis (63) TB and other respiratory infections (611)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
