Prescriptions of systemic antibiotics for children in Germany aged between 0 and 6 years

pharmacoepidemiology and drug safety 2003; 12: 113–120Published online 18 December 2002 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pds.786

ORIGINAL PAPER

Prescriptions of systemic antibiotics for children in Germanyaged between 0 and 6 years

Christoph Schindler, Jutta Krappweis, Ingolf Morgenstern and Wilhelm Kirch

Institute of Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany

SUMMARY

Limited information is available about systemic antibiotic use among children in Germany. We therefore assessed prescrip-tion patterns by office-based physicians to analyse antibiotic consumption in early childhood. A total of 331 children <6years were eligible for inclusion. The number of antibiotic prescriptions, consumed daily doses, number of treatmentcourses, types of antibiotics and diagnoses for prescribing were determined. The prevalence of systemic antibiotic treatmentwas 42.9%. Antibiotic consumption was highest between 2 and 3 years of age (55.8%). The percentage of children receivingone, two or three courses of antibiotic treatment was 49.3, 28.2 and 16.2%, respectively. Acute otitis media (32.2%), upperrespiratory tract infections (18.9%), tonsillitis (15.9%) and acute bronchitis (15.4%) were principal indications for treat-ment. Macrolides were most frequently prescribed (48.1%), followed by penicillin V (21.3%), broad-spectrum penicillins(14.3%), sulfonamides (10.5%) and cephalosporins (5.8%). Antibiotics not recommended for particular indication wereselected in 5–43% of cases. The considerable prescription of systemic antibiotics to children in many European countriesis also the case in Germany. A noteworthy trend emerged for suboptimal prescribing with second-line antibiotics. As suchtreatment may be associated with the development of bacterial resistance, improved guidelines for antibiotic treatmentshould be drawn up and enforced. Copyright # 2002 John Wiley & Sons, Ltd.

key words— antibiotic treatment; children; Germany; prescription patterns

abbreviations— defined daily dose (DDD)

INTRODUCTION

As infectious agents are responsible for the majority ofdiseases that arise during childhood, it is not surprisingthat antibiotics are the systemic drugs most frequentlyprescribed to children. The preponderant consumptionof this class of substances by young persons has beendocumented in numerous studies.1,3,5,9,12–15,17,18,20,22–25

For example, in one cross-sectional Dutch survey,18

60% of children between the ages of 0 and 16 werefound to have taken at least one drug during the 1-year

investigational period. Systemic antibiotics were con-sumed by 21% of these children—a percentage doublethat of the next most frequently prescribed drug classeswhich included analgesics (10%), dermatological cor-ticosteroids, (9%), H1 antihistamines (8%) and anti-asthmatics (7%). Similarly, a large-scale Danishepidemiological survey25 determined that no less thantwo-thirds of children aged 0–2 had been treated witheither a systemic or topical antibiotic in the 12-monthstudy. Another investigation carried out in Denmark12

indicated that the 1-year prescription rate of antibac-terials for systemic use decreased with age fromapproximately 63% for 1-year olds to 18% among12-year old children. The large majority of such drugs(83%) were prescribed by general practitioners. Unfor-tunately, many such studies have also documentedthe unnecessary, injudicious or excessive use of

Received 13 April 2002Revised 2 October 2002

Copyright # 2002 John Wiley & Sons, Ltd. Accepted 28 October 2002

* Correspondence to: Dr C. Schindler, Institute of ClinicalPharmacology, Medical Faculty, Technical University Dresden,Fiedlerstrasse 27, D-01307 Dresden, Germany.E-mail: [email protected]

antibiotics—practices that have led to an alarming risein antibiotic resistance that poses a major threat to pub-lic health worldwide.29

Despite widespread prescription of antibiotics tochildren, it would be incorrect to assume that theiruse in developed countries is homogeneous. Thiswas clearly demonstrated in a recent survey,6 whichshowed that the general sales of antibiotics inEuropean Union countries varied by a factor of four.When expressed in defined daily doses (DDD) per1000 persons per day, countries such as France(36.5), Spain (32.4) and Portugal (28.8) showed thehighest levels of outpatient antibiotic sales, whereasthe lowest figures were registered in the Netherlands(8.9), Denmark (11.3) and Sweden (13.5). It was alsoclear that there were significant variations in the con-sumption of different antibiotic subgroups among themember states surveyed.

With respect to Germany, national data derived fromthe statutory health insurance system in 1993 indicatedthat children aged 0–4 years consumed 7.4 DDD anti-biotics. This figure is higher than the 6.2, 3.2 and 0.5DDDs consumed for analgesics, H1 antihistaminesand antiemetics, respectively, but lower than the 62.6,33.4, 27.9 and 16.8 DDDs consumed for vitamins, rhi-nologics, antitussives and dermatological creams/pow-ders, respectively.21 However, the detailed analysis ofantibiotic prescription patterns in relation to such vari-ables as age, indication and types of antibiotics pre-scribed is patchy or even lacking on a national orregional basis. This is because investigations into anti-biotic use by children have been conducted on a rela-tively limited scale, confined to hospitals or smallercommunities, and have mostly been carried out in thewestern part of the country. We therefore conducted astudy in a large urban area located in the eastern part ofGermany to estimate the prevalence of systemic anti-biotic use in younger children.

METHODOLOGY

Setting

In Germany, population-related information on theprescribed use of drugs is only obtainable from therecords maintained by statutory health insurance orga-nisations. These groups ensure about 90% of theGerman population, and partially cover the costs ofall medical goods and services for their members.Of these organisations, the General Local HealthInsurance (Allgemeine Ortskrankenkasse, AOK)provided health coverage for nearly 50% of theDresden regional population (800 000 members) in

the 1993/1994 period. The remaining 50% of thepopulation was insured by a variety of statutory healthinsurances (e.g. company health insurance organisa-tions).

Design

The database used in the present study consisted of thehealth insurance files of AOK-Dresden members whowere insured on 1 July 1993. A population sample(primary insured, dependants, pensioners; n¼ 7490)was drawn from this database by a random generatorand was not stratified by age or gender. From thiscohort, 7011 persons were insured throughout theentire 1993/1994 calendar year. The study populationeligible for inclusion in the present survey was derivedfrom this latter sample and included all childrenbetween 0 and 6 years of age who had received at leastone prescription for a systemic antibiotic drug duringthe investigational period (1 July 1993–30 June 1994).

The health insurance files of these children werethen examined and relevant information was extrac-ted, computerised, linked and evaluated. We deter-mined the number of antibiotic prescriptions issued,the consumed daily doses of antibiotics, the numberof treatment courses expressed as a proportion of thestudy population (stratified by age), the types of anti-biotics used and the diagnoses for prescribing. As theunit of drug consumption, we used the DDD—theassumed average drug dose for 24 hours for the corre-sponding indication in adults. The systemic antibio-tics (antimycotics excluded) were classified into fivegroups (penicillin V, broad-spectrum penicillins,macrolides, cephalosporins and sulfonamides) usingthe WHO Anatomical Therapeutic Chemical (ATC)classification system (ATC group J01). Fluoroquino-lones were not included in this study because inGermany they are not licensed for prescription in chil-dren and young adults due to potential cartilage toxi-city of this antibiotic class established in animal trials.Diagnoses were assigned according to the Interna-tional Classification of Disease, Tenth Revision(ICD-10). For data compilation and programming ofthe analysis procedure, a relational database was setup (Paradox 7.0, Borland International Corp., ScottsValley, CA).

RESULTS

Three hundred and thirty-one children aged 0–6 yearswere eligible for inclusion in our survey. Of these, 142children (42.9%) received at least one prescription fora systemic antibiotic (Table 1), with fewer males

114 c. schindler et al.

Copyright # 2002 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 2003; 12: 113–120

(n¼ 65) than females (n¼ 77) being issued such pre-scriptions. We identified a total of 258 prescriptionsfor these children (121 prescriptions to boys, 46.9%;137 to girls, 53.1%). When stratified by age(Figure 1), the proportion of children receiving sys-temic antibiotics was highest in the age group between2 and 3 years (55.8%), followed closely by those aged1–2 years (53.1%). Physicians wrote fewest such pre-scriptions to children under 1 year of age. Approxi-mately 40% of children in the three age bracketsfrom 3 to 6 years received systemic antibiotics. Dur-

ing the 1993/1994 period, 49.3, 28.2 and 16.2%received one, two or three prescriptions for antibiotictreatment, respectively (Table 2). With respect to anti-biotic consumption, 53.5, 32.4, 8.5 and 5.6% of trea-ted patients consumed 1–10, 11–20, 21–30, and >30DDDs, respectively. More than one third of patientsreceived prescriptions for two or more courses oftreatment (Table 3).

Of the 142 infants and children receiving systemicantibiotics, the most frequent indications for their use(Figure 2) were acute otitis media (32.2%) followed

Table 1. Study population and percent receiving systemicantibiotics

Age (years) Males Females Total No. receivingantibiotics (%)

0–2* 23 19 42 19 (45.2)2–3 30 22 52 29 (55.8)3–4 36 42 78 30 (38.5)4–5 48 40 88 35 (39.8)5–6 33 38 71 29 (40.8)Total 170 161 331 142 (42.9)

*As the age group 0–12 months consisted of only 2 children takingantibiotics (1 boy, 1 girl), this group was merged into the 17 children(9 boys, 8 girls) making up the group 1–2 years.

Figure 1. Proportion of children receiving antibiotics according to age and gender. Data from North Jutland study22 provided forcomparison

Table 2. Number of antibiotic prescriptions received

Prescriptions Saxony North Jutland*

per child (n) % (n) % (n)

1 49.3 (70) 57.7 (9374)2 28.2 (40) 24.6 (3996)3 16.2 (23) 10.8 (1754)4 4.9 (7) 4.9 (796)5 1.4 (2) 2.0 (325)

*Data from a very similar designed study with larger studypopulation performed by Thrane et al. in North Jutland, Denmark22

provided for comparison. The absolute numbers of children areprovided in brackets.

prescriptions of systemic antibiotics for children 115


by infections of the upper respiratory tract (18.9%),tonsillitis (15.9%) and acute bronchitis (15.4%). Noindication was mentioned for a prescription in 9%of all cases.

As seen in Figure 3, the children in our study popu-lation most frequently received macrolides (48.1%),followed by penicillin V (21.3%), broad-spectrumpenicillins (14.3%), sulfonamides (10.5%) and cepha-

losporins (5.8%). The distribution of antibiotic sub-groups with respect to the four most commonindications is shown in Figure 4. For otitis media,macrolides (70%) or aminopenicillins (11%) weremainly prescribed. Penicillin V was the principalagent prescribed for tonsillitis/scarlet fever (76%),with 13% of children receiving macrolides and 9%getting aminopenicillins. Children with upper respira-tory tract infections principally received prescriptionsfor macrolides (37%) and sulfonamides (25%), whilethose diagnosed with bronchitis were mostly pre-scribed macrolides (65%) and aminopenicillins(23%). Antibiotics not recommended for use or as sec-ond choice were selected in 5–43% of cases (Table 4),and were prescribed most egregiously for upperrespiratory infections (37%) and for bronchitis(43%). It should be noted that we have consideredthe use of erythromycin combinations (34%; e.g.

Table 3. Courses of antibiotic treatment (% treated patients)

No. treatment courses Saxony North Jutland*

1 62.0 63.42 26.1 24.03 9.9 8.94 1.4 2.95 0.7 0.8

*Data from North Jutland study22 provided for comparison.

Figure 2. Indications for prescription of antibiotic treatment to children aged 0–6 years



erythromycin plus antitussive) as not recommendablefor bronchitis (Table 4) versus the sole use of macro-lides (31%) because the therapeutic efficacy of expec-

torants as well as the pharmacological usefulness offixed combinations in general is discussed controver-sial.21 However, for purposes of clarity, macrolides(37%) and erythromycin combinations (5%) are listedtogether in Figure 4 (¼ 42%).

DISCUSSION

In order to determine the prescription patterns of anti-biotics issued to children by office-based physicians ina defined German population, we analysed the auto-mated records of prescriptions and file claims derivedfrom a large Dresden statutory health insurance orga-nisation. Such health insurance data may not alwaysbe completely representative of physician prescribinghabits and the consumption of the drugs in questionsince (i) the statutory health insurance organisationsdo not cover 10% of the German population, and (ii)the available data provides information on the numberof prescriptions purchased, but not on the actual con-sumption of the medication. Nevertheless, given thatmembers of statutory health insurances in Germanyreceived between 90% and 100% reimbursement perdrug purchased in 1994, it is quite likely that themajority of filled antibiotic prescriptions were

Figure 3. Distribution of principal antibiotic subgroups as a percentage of total antibiotic prescriptions

Table 4. Prescription patterns

Diagnosis Recommended Not recommended(actually prescribed) (actually prescribed)

Otitis media Aminopenicillins (11%) Sulfonamides (7%)Macrolides (70%) Penicillins (6%)Cephalosporins (6%)

Tonsillitis/ Penicillin V (76%) Aminopenicillinsscarlet fever (9%)*

Cephalosporins (2%)*Macrolides (13%)*

URTI Cephalosporins (12%) Sulfonamides (25%)Aminopenicillins (14%) Penicillins (7%)Macrolides (37%) Erythromycin

comb. (5%)þ

Bronchitis Cephalosporins (3%) Sulfonamides (9%)Aminopenicillins (23%) Erythromycin

comb. (34%)þ

Macrolides (31%)

*Second choice; þCombination of erythromycin plus antitussive.URTI, upper respiratory tract infection; recommendations accord-ing to an expert commission of the Paul-Ehrlich Institute forChemotherapy: Rational use of oral antibiotics in practice. MMW1998; 140: 118–127.



purchased on behalf of, and consumed by, theintended recipients. Of course one could criticise thata file based study does not reflect the individualpatient’s symptoms but this method is the only onepracticable to estimate prevalences in a large popula-tion for study purpose. Furthermore one could arguethat the sample of our study was rather small. There-fore we have to emphasise that our study population isa representative 1% random sample of all members ofthe statutory General Local Health Insurance Com-pany (AOK) in Saxony who were insured on 1 July1993. At that time no differences concerning age orsocial class were present within the different statutoryhealth insurance companies in Germany. Thereforethe sample is representative for all members of thestatutory health insurance system which covers themajority of the german population. However, differ-

ences between members of the statutory health insur-ance system and people insured in private companiescan not be excluded.

We found that the 1-year prevalence for antibiotictreatment in Saxony in 1993/1994 for childrenyounger than 6 years was 42.9%. This clearly indi-cates that the majority of younger children will even-tually be exposed to systemic antibiotics in the courseof childhood. Our results thereby accord with findingsin other European countries1,5,9,14,17,20,22–25 and else-where,3,13,15 namely that children are major consu-mers of systemic antibiotics, particularly thosebetween 1 and 3 years.1,15,20 Interestingly, a similarlydesigned Danish study carried out in North Jutland22

also revealed a treatment prevalence among childrenaged between 0 and 5 of 42.7%. Furthermore, of thoseprescribed antibiotics, 63.4% of the Danish children

Figure 4. Distribution (percent) of antibiotic subgroups used to treat the four most frequent indications among children 0–6 years of age



received one course of antibiotics compared to 62% inour investigation (Table 3). This also indicates thatin both countries, about 40% of these children weretreated at least twice. Such repeated antibiotic treat-ment courses in children, coupled with selectiveantimicrobial pressure, has been linked with the emer-gence of antimicrobial resistance patterns. This wasrecently demonstrated in an Icelandic study,1 wherebya strong association in children under the age of sevenwas found between nasopharyngeal carriage of peni-cillin-resistant pneumococci and the total antimicro-bial consumption in the surveyed communities. Thethreat posed by multidrug-resistant bacterial strainsis not confined to the developed countries, but hasarisen in the developing world as well, especiallywhere antibiotics are available without doctors’ pre-scriptions.14

While macrolides (48%) and penicillin (21%) werefound to be the antibiotics most commonly prescribedin Saxony, this is not necessarily the case in otherEuropean countries. For instance, in Denmark, physi-cians mainly prescribed broad-spectrum penicillins(49%) and penicillin V (38%) to children between 0and 5 years of age.22 But it also should not be forgot-ten that antibiotic usage patterns may also vary fromcountry to country due to differences in the spectrumof the pathogens present.

We also confirmed the widespread prescription ofantibiotics to patients with such conditions as acuteotitis media, upper respiratory tract infections, tonsil-litis and acute bronchitis. Many studies have pointedout that antibiotics need not be prescribed for suchindications due to the viral etiology of the vast major-ity of these infections.2,14,20 A recent evidence-basedstudy found that 80% of cases of acute otitis mediaresolved without antibiotic treatment.16 Furthermore,the seasonal coincidence of upper respiratory infec-tions and acute otitis media clearly points to the pre-ponderant causative role of viruses for this lattercondition.26 Nevertheless, several investigations,14,15

including our own, continue to demonstrate the extentto which children who present with otitis media, ton-sillitis or bronchitis continue to receive antibiotics,despite evidence that such treatment fails to improvethe outcomes for these patients.2,10,11 It appears to bethe general practitioner, and not the paediatrician, whois responsible for the inordinately large number ofantibiotic prescriptions for such conditions,19 espe-cially for their prescriptions of broad-spectrum anti-biotics.2,15 Our results not only demonstrate thewidespread overprescription of antibiotics to children,but also confirm that many antibiotic drugs are routi-nely prescribed which are not recommended for the

corresponding indication. In Germany, the PaulEhrlich Society publishes recommendations for anti-biotic treatment.27 According to their guidelines foracute otitis media, no antibiotics should be initiallyprescribed. The physician should adopt a wait-and-watch attitude to see if the condition resolves sponta-neously. But if antibiotics should ultimately provenecessary due to bacterial complications (commonlycaused in children by pneumococci), cephalosporins(except third generation), aminopenicillins plus clavu-lanic acid or macrolides should be administered.However, we found that macrolides were being pre-scribed (70%) far and above aminopenicillins (11%)and cephalosporins (6%). When acute bacterial mid-dle ear infections do occur in young children inGermany, we rather suggest the use of amoxicillinplus clavulanic acid as first-line therapy, macrolidesas second-line agents, and cephalosporins reservedfor third-line use [see also ref. 4].

For tonsillitis resulting from streptococcal infec-tion, penicillin is still recommended as first-line treat-ment; macrolides and cephalosporins can be usedalternatively. We observed that penicillin V, macro-lides and cephalosporins were being prescribed in76, 13 and 2% of cases, respectively. Aminopenicil-lins (amoxicillin or ampicillin) were prescribed tonearly 9% of children. Their use is justified in casesof superinfection by haemophilus influenzae. The fre-quent use of macrolides for childhood infections isprobably a practical consequence of the better tasteof macrolide-containing syrups.

In order to counteract the increasing problems posedby multiresistant bacteria, physicians should carefullyreconsider their prescribing behaviour with respect tothe use of systemic antibiotics in children. This espe-cially applies to the injudicious use of broad-spectrumantibiotics in many cases, and to the prescription ofantibiotics for influenza to infants and very young chil-dren. Not only does the excessive use of antibioticspromote the emergence of multiresistant bacteria, butalso increases the risk for the development of asthmaand atopic disorders in children.7,8,28

Taking into account that our study is a file basedstudy, conclusions have to be drawn very carefully.We found that the noteworthy trend towards multipleand often suboptimal prescription of systemic antibio-tics to children in many European countries is also thecase for children in Germany. This trend should leadto careful reconsideration of antibiotic prescribingpolicy to children. Furthermore the results of ourstudy support the need for improved standardisedguidelines concerning the prescription of antibiotictherapy for infectious diseases in childhood.



REFERENCES

1. Arason VA, Kristinsson KG, Sigurdsson JA, Stefansdottir G,Molstad S, Gudmundsson S. Do antimicrobials increase thecarriage rate of penicillin resistant pneumococci in children?Cross sectional prevalence study. BMJ 1996; 313: 387–391.

2. Aronoff SC. Antimicrobials in children and the problem ofdrug resistance. Am Fam Phys 1996; 54: 44, 46, 54, 55.

3. Bergus GR, Levy BT, Levy SM, Slager SL, Kiritsy MC.Antibiotic use during the first 200 days of life. Arch FamMed 1996; 5: 523–526.

4. Bergus GR, Levy SM, Kirchner HL, Warren JJ, Levy BT. Aprospective study of antibiotic use and associated infectionsin young children. Pediatr Perinat Epidemiol 2001; 15: 61–67.

5. Calvo Rey C, Albanil Ballesteros R, Sanchez Mendez MY, Oli-vas Dominguez A. Antibiotic prescribing habits in primaryhealth care: do pediatricians use antibiotics rationally? AnEsp Pediatr 2000; 52: 157–163.

6. Cars O, Molstad S, Melander A. Variation in antibiotic use inthe European Union. Lancet 2001; 357: 1851–1853.

7. Droste JHJ, Wieringa MH, Weyler JJ, Nelen VJ, Vermeire PA,van Bever HP. Does the use of antibiotics in early childhoodincrease the risk of asthma and allergic disease? Clin ExpAllergy 2000; 30: 1547–1553.

8. Farooqi IS, Hopkin JM. Early childhood infection and atopicdisorder. Thorax 1998; 53: 927–932.

9. Guillemot D, Carbon C, Vauzelle-Kervroedan F, Balkau B,Maison P, Bouvenot G, Eschwege E. Inappropriateness andvariability of antibiotic prescription among French office-based physicians. J Clin Epidemiol 1998; 51: 61–68.

10. Hamm RM, Hicks RJ, Bemben DA. Antibiotics and respiratoryinfections: do antibiotic prescriptions improve outcomes?J Okla State Med Assoc 1996; 89: 267–274.

11. Hueston WJ, Hopper JE, Dacus EN, Mainous AG, III. Why areantibiotics prescribed for patients with acute bronchitis? Apostintervention analysis. J Am Board Fam Pract 2000; 13:398–402.

12. Johansen HL, Kampmann JM, Ingradsen BK. Use of antibio-tics among Danish children in 1998. Consumption on anational basis. Ugeskr Laeger 2000; 162: 2028–2031.

13. Larsson M, Kronvall G, Chuc N, Karlsson I, Lager F, Hanh H,Tomson G, Falkenberg T. Antibiotic medication and bacterialresistance to antibiotics: a survey of children in a Vietnamesecommunity. Trop Med Int Health 2000; 5: 711–721.

14. Myrbakk T, Giaever A, Olsvik O, Flaegstad T. Antibiotic treat-ment of acute otitis in children. Tidsskr Nor Laegeforen 1999;10: 119.

15. Nyquist AC, Gonzales R, Steiner JF, Sande MA. Antibioticprescribing for children with colds, upper respiratory tractinfections, and bronchitis. JAMA 1998; 279: 875–877.

16. O’Neill P. Acute otitis media. BMJ 1999; 319: 350–354.17. Rasmussen F. Use of antibiotics and prescription drugs in gen-

eral during the first 9 years of life in a Swedish community.Paediatr Perinat Epidemiol 1988; 2: 346–358.

18. Schirm E, van den Berg P, Gebben H, Sauer P, de Jong-van denBerg L. Drug use of children in the community assessedthrough pharmacy dispensing data. Br J Clin Pharmacol2000; 50: 473–478.

19. Steffensen FH, Schonheyder HC, Sorensen HAT. High prescri-bers of antibiotics among general practitioners—relation toprescribing habits of other drugs and use of microbiologicaldiagnostics. Scand J Infect Dis 1997; 29: 409–413.

20. Straand J, Rokstad K, Heggedal U. Drug prescribing for chil-dren in general practice. A report from the Møre & RomsdalPrescription Study. Acta Paediatr 1998; 87: 218–224.

21. Schwabe U, Paffrath D. Arzneiverordnungs-Report 1993. Gus-tav Fischer Verlag: Berlin, 1994.

22. Thrane N, Olesena C, Schonheyder HC, Sorensen HAT. Multi-ple prescriptions of antibiotics for children aged 0–5 years inrelation to type of antibiotic. J Antimicrob Chemother 1999;44: 839–842.

23. Thrane N, Sorensen HAT. A one-year population-based studyof drug prescriptions for Danish children. Acta Paediatr 1999;88: 1131–1136.

24. Thrane N, Sorensen HAT. Drug prescriptions for Danish chil-dren. Ugeskr Laeger 2000; 162: 3460–3464.

25. Thrane N, Steffensen FH, Mortensen JT, Schonheyder HC,Sorensen HAT. A population-based study of antibiotic pre-scriptions for Danish children. Pediatr Infect Dis J 1999; 18:333–337.

26. Vesa S, Kleemola M, Blomquvist S, Takala A, Kilpi T, Hovi T.Epidemiology of documented viral respiratory infections andacute otitis media in a cohort of children followed from twoto twenty-four months of age. Pediatr Infect Dis J 2001; 20:574–581.

27. Vogel F, Worth H, Adam D, Elies W, Ewig S, Hoffken G,Lode H, Lorenz J, Scholz H, Stille W, Unertl K, WiedermannB. Rationale Therapie bakterieller Atemwegsinfektionen.Chemother J 2000; 1: 19–20.

28. Wickens K, Pearce N, Crane J, Beasly R. Antibiotic use inearly childhood and the development of asthma. Clin ExpAllergy 1999; 29: 766–771.

29. Wise R, Hart T, Cars O. Antimicrobial resistance is a majorthreat to public health. BMJ 1998; 317: 609–610.



Documents

Prescriptions of systemic antibiotics for children in Germany aged between 0 and 6 years